MyoD和Cx43基因诱导成纤维细胞分化为肌细胞及其对心肌梗死后心功能的影响
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摘要
研究背景:
众所周知,成年人的心肌细胞在病理状态下缺乏分裂增值能力,缺血性心脏病如急性心肌梗死(acute myocardial infarction,AMI)所致的心肌细胞丢失和瘢痕形成是导致顽固性心力衰竭乃至死亡的病理基础。目前,以培养的收缩性体细胞作为“补片”种植于受损心肌疤痕组织中进行心肌重建的细胞性心肌成形术(cellular cardiomyoplasty,CCM)被认为是一种很有前景的治疗手段。实施CCM需要解决的首要问题就是如何获得大量合适的可移植细胞。虽然将体外培养的心肌细胞、骨骼肌卫星细胞、骨髓干细胞及胚胎干细胞等移植到心肌梗死后的疤痕组织中能够一定程度上改善心功能,但因自身存在的缺陷而限制了临床应用。生肌调节因子(myogenic determination,MyoD)基因是肌肉发生的主导调控基因,能够启动和促进包括成纤维细胞在内多种非肌细胞的肌生成。此外,CCM技术需要解决的另一个关键性问题就是如何实现移植细胞与原有心肌细胞之间的功能整合,这得依赖于移植细胞与原有心肌细胞之间缝隙连接介导的细胞间通讯(gap junctional intercellular communication,GJIC),连接蛋白43(connexin 43,Cx43)基因表达可以使细胞之间的GJIC形成。近年来的研究表明通过基因工程将成纤维细胞改造成为可兴奋细胞是可能的;而真皮成纤维细胞(dermal fibroblast,DFs)是机体内数量最大的“种子细胞库”,因此,将组织工程技术与转基因技术相结合,通过MyoD和Cx43基因诱导DFs分化为具有GJIC功能的“心肌样”肌细胞,有望成为CCM一种新的“种子细胞”来源。
目的:
探讨体外MyoD和Cx43基因诱导大鼠DFs分化为“心肌样”肌细胞的生物学特性,并将其自体心肌局部注射移植至AMI大鼠的心肌梗死区内,观察心肌结构和心功能的变化。
方法:
(1)采用Ⅱ型胶原蛋白酶分离、培养大鼠DFs,并观察其体外生长的生物学特性;
(2)构建携带大鼠MyoD和Cx43基因的真核表达质粒载体pLenti6/v5-DESTMyoD和pLenti6/v5-DEST-Cx43,并通过电泳和测序加以鉴定;
(3)利用慢病毒表达系统,将MyoD和Cx43基因转染体外培养的DFs,诱导其分化为“心肌样”肌细胞;
(4)观察MyoD和Cx43基因转染DFs后细胞形态学及超微结构的变化,并通过分子生物学手段确定MyoD和Cx43基因的转录与表达情况;
(5)采取开胸术式结扎大鼠左冠状动脉前降支(left anterior descending coronaryartery,LAD)的方法建立大鼠AMI模型;
(6)将体外诱导分化成功的“心肌样”肌细胞通过局部注射自体心肌移植到AMI大鼠的心肌梗死区内;
(7)在细胞移植前和移植后4周内观察心电图和血浆脑钠素(BNP)浓度的变化;
(8)于细胞移植4周后采用Langendorff离体心脏灌流和多外围设备转接器(MPA)信号采集分析系统评价大鼠左心室功能的变化,同时采用染色法测定心肌梗死面积(myocardial infarction size,MIS);
(9)应用免疫组织化学技术检测5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,BrdU)标记移植细胞在宿主心肌内的驻留存活及其connexin43蛋白的分布情况;
(10)通过透射电子显微镜观察移植区内细胞的超微结构和缝隙连接形成情况。
结果:
(1)成功建立了高纯度大鼠DFs的体外培养模型,纯度达95%以上,波形蛋白免疫细胞染色为阳性;
(2)电泳和测序结果证实已成功将大鼠MyoD和Cx43基因的全长序列cDNA片段克隆到慢病毒载体中,成功构建了真核表达载体pLenti6/v5-DEST-MyoD和pLenti6/v5-DEST-Cx43;
(3)RT-PCR和Western blot检测出基因转染后细胞表达了MyoD和Cx43基因相应的产物;
(4)免疫细胞化学检测显示MyoD基因转染成功的细胞肌动蛋白、结蛋白呈阳性及电子显微镜观察到Cx43基因转染成功的细胞间有缝隙连接形成;
(5)通过结扎LAD,4周后能够形成梗死部位和MIS稳定的大鼠AMI模型;
(6)细胞移植术后4周,MyoD和Cx43基因联合转染DFs诱导分化成功的“心肌样”肌细胞自体心肌内移植后,可以减少AMI大鼠的MIS、降低血浆BNP浓度、改善心脏的缩舒功能及心电图的异常程度;
(7)免疫组织化学检测显示心肌梗死瘢痕区及边缘处细胞移植后有BrdU阳性细胞存在和connexin43蛋白分布;
(8)MyoD和Cx43基因联合转染DFs诱导分化成功的“心肌样”肌细胞于心肌内移植后,透射电子显微镜下可观察到这些细胞之间有缝隙连接形成。
结论:
(1)MyoD和Cx43基因可以成功诱导体外培养的DFs分化为“心肌样”肌细胞;
(2)这种分化成功的“心肌样”肌细胞经自体心肌移植后能够在宿主体内生长、增殖,并可在一定程度上减轻AMI大鼠心室重构的进程及改善心功能,且这种经心外膜途径移植是安全可行的。
Backgrounds:
The dogma of the heart as an organ composed of terminally differentiated myocytes incapable of regeneration, which endogenous repair mechanisms are overwhelmed in patients with acute myocardial infarction (AMI), advanced coronary artery disease, and chronic heart failure, is being challenged. Cellular cardiomyo-plasty (CCM) by cell transplantation is a promising strategy that offers the creation of new functional tissue to replace lost or failing myocardium. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. Several cell sources have been tested, although each of them entails considerable limitations. The myogenic determination (MyoD, a skeletal myogenic determination factor) as unique master genes that are able to prompt myogenesis in a variety of cells including fibroblasts. Transformation of cardiac fibroblasts in situ into skeletal myocytes in myocardial infarct scar tissue could add to postinfarction adaptation. However, attempts to convert the infarcted myocardium into contractile tissue in situ by direct injection of viral vectors encoding the MyoD required a high dose of recombinant adenovirus, and yielded disappointing results. The essential physiological properties of between cardiomyocytes and grafted cells supporting efficient myocardial impulse propagation are an excitable cell membrane and capacity for gap junctional intercellular communication (GJIC), and the capacity for GJIC through expression of connexin43 (Cx43), a gap junction protein. Evidence has been presented that fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling, and the dermal fibroblast (DFs) from skin was an alternative source of autologous cells. Ex vivo cellular cardiomyoplasty is an alternative myocardial repair strategy that combines the advances in genetic and tissue engineering. This approach may provide an alternative source of autologous, transplantable, myogenic cells by ex vivo genetic manipulation of the fibroblasts. The aim of our study was, therefore, to address the issue of whether the phenomenon of myogenic conversion of autologous DFs with both MyoD and Cx43 genes could be exploited in practical terms to provide an alternative source of myogenic cells for transplantation.
Objective:
The purpose of our study was to determine whether the phenotype of both MyoD and Cx43 genes could induce autologous DFs to produce myoblasts capable of gap junction coupling -- "cardiac-like myocytes" ex vivo, and the influence of the converted cells on myocardial structure and cardiac function after being implantated into acute infarcted myocardial site in rats in a clinically relevant approach.
Methods:
(1) Explore the biological characteristics of DFs isolated and cultured from the skin dermal tissue of Sprague-Dawley (SD) rats by digesting with collagenase type II ex vivo;
(2) Construct efficient eukaryotic expression plasmid lentiviral vector pLenti6/v5-DEST-MyoD and pLenti6/v5-DEST-Cx43 encoding exogenetic rat MyoD cDNA or Cx43 cDNA respectively, which were identified with the agarose electrophoresis and sequent examination;
(3) The cultured rat DFs were transfected with the recombinant eukaryotic expression lentiviral vector with lipotransfection method according to lentiviral expression system protocol;
(4) The mophological and ultrastructure changes of these transfected cells by MyoD &/or Cx43 genes ex vivo were observed by microscopy, and the expression of MyoD and Cx43 genes in the transfected cells was detected by immunocyto-chemical methods;
(5) Rat AMI models were established by ligating the middle-proximal 1/3 segment of left anterior descending coronary artery (LAD);
(6) The converted cells (2.0×10~6) were autologous transplanted into the infarcted myocardium four weeks after coronary artery occlusion;
(7) The changes of electrocardiogram (ECG) was observed by multiple peripheral adapter (MPA) physiologic recorder system, and plasma B-type natriuretic peptide (BNP) concentration were measured during perioperation of cell transplantation;
(8) Four weeks later after cell transplantation, cardiac function of left ventricular were evaluated by Langendorff perfusion of the isolated heart instrument with MPA physiologic recorder system, and myocardial infarction size (MIS) were be detected by 2,3,5-triphenyltetrazolium chloride (TTC) method;
(9) The bromodeoxyuridine (BrdU)-labeled immunohistochemistry was used to observe grafted cells differentiation and development in vivo, and connexin43 immunohistochemistry studies were performed to assess the function of these implantated cells;
(10) Ultrastructure and typical cross gap junction of the grafted cells in infarcted myocardium were characterized by transmission electron microscopy.
Results:
(1) The model of rat DFs culture was successfully established with high purity(> 95%) ex vivo, and immunostaining of vimentin was positive in cultured DFs;
(2) The MyoD cDNA or Cx43 cDNA were cloned into Lentiviral vector respectively, and the cDNA sequencing results of pLenti6/v5-DEST-MyoD and pLenti6/v5- DEST-Cx43 were identified with the agarose electrophoresis and sequent examination;
(3) These transfected cells were detected out the expression of MyoD and Cx43 genes by RT-PCR and Western blot;
(4) The efficiented transduced DFs with the MyoD and Cx43-encoding vector underwent myogenic conversion, as evidenced by the positive immunostaining of immunocytochemical methods for desmin and alpha-actin, and detection of typical cross gap junction coupling in these adjacent converted DFs by electron microscopy;
(5) A standard rat AMI model, which MIS was invariableness could be created by surgical ligation of LAD;
(6) By four weeks after the converted DFs by MyoD and Cx43 genes myocardial transplantation, the MIS and BNP in accepted myocardial transplantation group were lower than that in other control groups, and the dysfunctional ECG and cardial function also improved in the same myocardial transplantation group;
(7) Histological study showed that grafted cells in infarcted myocardium were detected in all host hearts and identified by BrdU-labeled immunocytochemistry staining in the trial groups, and the gap junctions protein could be detected by connexin43 immunocytochemistry;
(8) After myocardial transplantation, DFs converted by both MyoD and Cx43 genes could be confluenced cardiac myocytes in original myocardium tissue, which gap junctional coupling emerged, were observed by electron microscopy.
Conclusions:
(1) DFs can be genetically modified by both MyoD and Cx43 genes to differentiate into "cardiac-like myocytes" capable of gap junction coupling ex vivo and to create a vast source of autologous myogenic cells for CCM;
(2) The DFs converted by both MyoD and Cx43 genes implantation can survive in the hosts' myocardial scar tissue, and be believed to attenuate the ventricular remodeling process and improve heart function significantly after auto-transplantation in AMI rats, which is a safe and has comprehensive curative effective method.
众所周知,成年人的心肌细胞在病理状态下缺乏分裂增值能力,缺血性心脏病如急性心肌梗死(acute myocardial infarction,AMI)所致的心肌细胞丢失和瘢痕形成是导致顽固性心力衰竭乃至死亡的病理基础。目前,以培养的收缩性体细胞作为“补片”种植于受损心肌疤痕组织中进行心肌重建的细胞性心肌成形术(cellular cardiomyoplasty,CCM)被认为是一种很有前景的治疗手段。实施CCM需要解决的首要问题就是如何获得大量合适的可移植细胞。虽然将体外培养的心肌细胞、骨骼肌卫星细胞、骨髓干细胞及胚胎干细胞等移植到心肌梗死后的疤痕组织中能够一定程度上改善心功能,但因自身存在的缺陷而限制了临床应用。生肌调节因子(myogenic determination,MyoD)基因是肌肉发生的主导调控基因,能够启动和促进包括成纤维细胞在内多种非肌细胞的肌生成。此外,CCM技术需要解决的另一个关键性问题就是如何实现移植细胞与原有心肌细胞之间的功能整合,这得依赖于移植细胞与原有心肌细胞之间缝隙连接介导的细胞间通讯(gap junctional intercellular communication,GJIC),连接蛋白43(connexin 43,Cx43)基因表达可以使细胞之间的GJIC形成。近年来的研究表明通过基因工程将成纤维细胞改造成为可兴奋细胞是可能的;而真皮成纤维细胞(dermal fibroblast,DFs)是机体内数量最大的“种子细胞库”,因此,将组织工程技术与转基因技术相结合,通过MyoD和Cx43基因诱导DFs分化为具有GJIC功能的“心肌样”肌细胞,有望成为CCM一种新的“种子细胞”来源。
目的:
探讨体外MyoD和Cx43基因诱导大鼠DFs分化为“心肌样”肌细胞的生物学特性,并将其自体心肌局部注射移植至AMI大鼠的心肌梗死区内,观察心肌结构和心功能的变化。
方法:
(1)采用Ⅱ型胶原蛋白酶分离、培养大鼠DFs,并观察其体外生长的生物学特性;
(2)构建携带大鼠MyoD和Cx43基因的真核表达质粒载体pLenti6/v5-DESTMyoD和pLenti6/v5-DEST-Cx43,并通过电泳和测序加以鉴定;
(3)利用慢病毒表达系统,将MyoD和Cx43基因转染体外培养的DFs,诱导其分化为“心肌样”肌细胞;
(4)观察MyoD和Cx43基因转染DFs后细胞形态学及超微结构的变化,并通过分子生物学手段确定MyoD和Cx43基因的转录与表达情况;
(5)采取开胸术式结扎大鼠左冠状动脉前降支(left anterior descending coronaryartery,LAD)的方法建立大鼠AMI模型;
(6)将体外诱导分化成功的“心肌样”肌细胞通过局部注射自体心肌移植到AMI大鼠的心肌梗死区内;
(7)在细胞移植前和移植后4周内观察心电图和血浆脑钠素(BNP)浓度的变化;
(8)于细胞移植4周后采用Langendorff离体心脏灌流和多外围设备转接器(MPA)信号采集分析系统评价大鼠左心室功能的变化,同时采用染色法测定心肌梗死面积(myocardial infarction size,MIS);
(9)应用免疫组织化学技术检测5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,BrdU)标记移植细胞在宿主心肌内的驻留存活及其connexin43蛋白的分布情况;
(10)通过透射电子显微镜观察移植区内细胞的超微结构和缝隙连接形成情况。
结果:
(1)成功建立了高纯度大鼠DFs的体外培养模型,纯度达95%以上,波形蛋白免疫细胞染色为阳性;
(2)电泳和测序结果证实已成功将大鼠MyoD和Cx43基因的全长序列cDNA片段克隆到慢病毒载体中,成功构建了真核表达载体pLenti6/v5-DEST-MyoD和pLenti6/v5-DEST-Cx43;
(3)RT-PCR和Western blot检测出基因转染后细胞表达了MyoD和Cx43基因相应的产物;
(4)免疫细胞化学检测显示MyoD基因转染成功的细胞肌动蛋白、结蛋白呈阳性及电子显微镜观察到Cx43基因转染成功的细胞间有缝隙连接形成;
(5)通过结扎LAD,4周后能够形成梗死部位和MIS稳定的大鼠AMI模型;
(6)细胞移植术后4周,MyoD和Cx43基因联合转染DFs诱导分化成功的“心肌样”肌细胞自体心肌内移植后,可以减少AMI大鼠的MIS、降低血浆BNP浓度、改善心脏的缩舒功能及心电图的异常程度;
(7)免疫组织化学检测显示心肌梗死瘢痕区及边缘处细胞移植后有BrdU阳性细胞存在和connexin43蛋白分布;
(8)MyoD和Cx43基因联合转染DFs诱导分化成功的“心肌样”肌细胞于心肌内移植后,透射电子显微镜下可观察到这些细胞之间有缝隙连接形成。
结论:
(1)MyoD和Cx43基因可以成功诱导体外培养的DFs分化为“心肌样”肌细胞;
(2)这种分化成功的“心肌样”肌细胞经自体心肌移植后能够在宿主体内生长、增殖,并可在一定程度上减轻AMI大鼠心室重构的进程及改善心功能,且这种经心外膜途径移植是安全可行的。
Backgrounds:
The dogma of the heart as an organ composed of terminally differentiated myocytes incapable of regeneration, which endogenous repair mechanisms are overwhelmed in patients with acute myocardial infarction (AMI), advanced coronary artery disease, and chronic heart failure, is being challenged. Cellular cardiomyo-plasty (CCM) by cell transplantation is a promising strategy that offers the creation of new functional tissue to replace lost or failing myocardium. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. Several cell sources have been tested, although each of them entails considerable limitations. The myogenic determination (MyoD, a skeletal myogenic determination factor) as unique master genes that are able to prompt myogenesis in a variety of cells including fibroblasts. Transformation of cardiac fibroblasts in situ into skeletal myocytes in myocardial infarct scar tissue could add to postinfarction adaptation. However, attempts to convert the infarcted myocardium into contractile tissue in situ by direct injection of viral vectors encoding the MyoD required a high dose of recombinant adenovirus, and yielded disappointing results. The essential physiological properties of between cardiomyocytes and grafted cells supporting efficient myocardial impulse propagation are an excitable cell membrane and capacity for gap junctional intercellular communication (GJIC), and the capacity for GJIC through expression of connexin43 (Cx43), a gap junction protein. Evidence has been presented that fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling, and the dermal fibroblast (DFs) from skin was an alternative source of autologous cells. Ex vivo cellular cardiomyoplasty is an alternative myocardial repair strategy that combines the advances in genetic and tissue engineering. This approach may provide an alternative source of autologous, transplantable, myogenic cells by ex vivo genetic manipulation of the fibroblasts. The aim of our study was, therefore, to address the issue of whether the phenomenon of myogenic conversion of autologous DFs with both MyoD and Cx43 genes could be exploited in practical terms to provide an alternative source of myogenic cells for transplantation.
Objective:
The purpose of our study was to determine whether the phenotype of both MyoD and Cx43 genes could induce autologous DFs to produce myoblasts capable of gap junction coupling -- "cardiac-like myocytes" ex vivo, and the influence of the converted cells on myocardial structure and cardiac function after being implantated into acute infarcted myocardial site in rats in a clinically relevant approach.
Methods:
(1) Explore the biological characteristics of DFs isolated and cultured from the skin dermal tissue of Sprague-Dawley (SD) rats by digesting with collagenase type II ex vivo;
(2) Construct efficient eukaryotic expression plasmid lentiviral vector pLenti6/v5-DEST-MyoD and pLenti6/v5-DEST-Cx43 encoding exogenetic rat MyoD cDNA or Cx43 cDNA respectively, which were identified with the agarose electrophoresis and sequent examination;
(3) The cultured rat DFs were transfected with the recombinant eukaryotic expression lentiviral vector with lipotransfection method according to lentiviral expression system protocol;
(4) The mophological and ultrastructure changes of these transfected cells by MyoD &/or Cx43 genes ex vivo were observed by microscopy, and the expression of MyoD and Cx43 genes in the transfected cells was detected by immunocyto-chemical methods;
(5) Rat AMI models were established by ligating the middle-proximal 1/3 segment of left anterior descending coronary artery (LAD);
(6) The converted cells (2.0×10~6) were autologous transplanted into the infarcted myocardium four weeks after coronary artery occlusion;
(7) The changes of electrocardiogram (ECG) was observed by multiple peripheral adapter (MPA) physiologic recorder system, and plasma B-type natriuretic peptide (BNP) concentration were measured during perioperation of cell transplantation;
(8) Four weeks later after cell transplantation, cardiac function of left ventricular were evaluated by Langendorff perfusion of the isolated heart instrument with MPA physiologic recorder system, and myocardial infarction size (MIS) were be detected by 2,3,5-triphenyltetrazolium chloride (TTC) method;
(9) The bromodeoxyuridine (BrdU)-labeled immunohistochemistry was used to observe grafted cells differentiation and development in vivo, and connexin43 immunohistochemistry studies were performed to assess the function of these implantated cells;
(10) Ultrastructure and typical cross gap junction of the grafted cells in infarcted myocardium were characterized by transmission electron microscopy.
Results:
(1) The model of rat DFs culture was successfully established with high purity(> 95%) ex vivo, and immunostaining of vimentin was positive in cultured DFs;
(2) The MyoD cDNA or Cx43 cDNA were cloned into Lentiviral vector respectively, and the cDNA sequencing results of pLenti6/v5-DEST-MyoD and pLenti6/v5- DEST-Cx43 were identified with the agarose electrophoresis and sequent examination;
(3) These transfected cells were detected out the expression of MyoD and Cx43 genes by RT-PCR and Western blot;
(4) The efficiented transduced DFs with the MyoD and Cx43-encoding vector underwent myogenic conversion, as evidenced by the positive immunostaining of immunocytochemical methods for desmin and alpha-actin, and detection of typical cross gap junction coupling in these adjacent converted DFs by electron microscopy;
(5) A standard rat AMI model, which MIS was invariableness could be created by surgical ligation of LAD;
(6) By four weeks after the converted DFs by MyoD and Cx43 genes myocardial transplantation, the MIS and BNP in accepted myocardial transplantation group were lower than that in other control groups, and the dysfunctional ECG and cardial function also improved in the same myocardial transplantation group;
(7) Histological study showed that grafted cells in infarcted myocardium were detected in all host hearts and identified by BrdU-labeled immunocytochemistry staining in the trial groups, and the gap junctions protein could be detected by connexin43 immunocytochemistry;
(8) After myocardial transplantation, DFs converted by both MyoD and Cx43 genes could be confluenced cardiac myocytes in original myocardium tissue, which gap junctional coupling emerged, were observed by electron microscopy.
Conclusions:
(1) DFs can be genetically modified by both MyoD and Cx43 genes to differentiate into "cardiac-like myocytes" capable of gap junction coupling ex vivo and to create a vast source of autologous myogenic cells for CCM;
(2) The DFs converted by both MyoD and Cx43 genes implantation can survive in the hosts' myocardial scar tissue, and be believed to attenuate the ventricular remodeling process and improve heart function significantly after auto-transplantation in AMI rats, which is a safe and has comprehensive curative effective method.
引文
[1] Nishina T, Nishimura K, Yuasa S, et al. Initial effects of the left ventricular repair by plication may not last long in a rat ischemic cardiomyopathy model [J]. Circulation, 2001, 104(12 Suppl 1): 1241-245.
[2] Bolognese L, Neskovic AN, Parodi G, et al. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications [J]. Circulation, 2002,106(18): 2351-2357.
[3] Hughes S. Cardiac stem cells [J]. J Pathol, 2002,197(4): 468-478.
[4] Soonpaa MH, Koh GY, Klug MG, et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium [J]. Science, 1994,264(5155): 98-101.
[5] Barile L, Chimenti I, Gaetani R, et al. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration [J]. Nat Clin Pract Cardiovasc Med, 2007, Suppl 1(S1): S9-S14.
[6] Chachques JC, Salanson-Lajos C, Lajos P, et al. Cellular cardiomyoplasty for myocardial regeneration [J]. Asian Cardiovasc Thorac Ann, 2005,13(3): 287-296.
[7] Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes [J]. Circ Res, 2002,91(3): 189-201.
[8] Burashnikov A, Antzelevitch C. Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations [J]. J Cardiovasc Electrophysiol, 2002,13(2): 172-177.
[9] Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up [J]. J Am Coll Cardiol, 2003,42(12): 2063-2069.
[10] Siminiak T, Kalawski R, Fiszer D, et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up [J]. Am Heart J, 2004, 148(3): 531-537.
[11] Bonaros N, Bernecker O, Ott H, et al. Cell- and gene therapy for ischemic heart disease [J]. Minerva Cardioangiol, 2005, 53(4): 265-273.
[12] Dedkov EI, Kostrominova TY, Borisov AB, et al. MyoD and myogenin protein expression in skeletal muscles of senile rats [J]. Cell Tissue Res, 2003, 311(3): 401-416.
[13] Suzuki K, Brand NJ, Allen S, et al. Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart [J]. J Thorac Cardiovasc Surg, 2001, 122(4): 759-766.
[14]范慧敏,汪进益,刘中民,等.Cx43转基因自体成肌细胞移植对犬急性心肌梗死后心肌结构和心功能的影响[J].中华实验外科杂志,2006,23(11):1328-1330.
[15]Etzion S,Barbash IM,Feinberg MS,et al.Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo:an unlimited source of cells for myocardial repair[J].Circulation,2002,106(12 Suppl 1):I125-130.
[16]汪进益,范慧敏,刘中民,等.大鼠皮肤成纤维细胞MyoD cDNA转染后的形态变化[J].同济大学学报(医学版),2007,28(1):6-9.
[17]Kizana E,Ginn SL,Allen DG,et al.Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling[J].Circulation,2005,111(4):394-398.
[18]崔磊,尹烁,邓辰亮,等.软骨形态发生蛋白1诱导真皮成纤维细胞向软骨细胞表型分化的影响因素[J].中华医学杂志,2005,85(33):2331-2337.
[19]唐佩弦.干细胞基础研究的新进展[J].基础医学与临床,2006,6(1):1-11.
[20]Marusic A,Katavic V,Grcevic D.Genetic variability of new bone induction in mice[J].Bone,1999,25(1):25-32.
[21]Moulin V,Castilloux G,Jean A,et al.In vitro models to study wound healing fibroblasts[J].Burns,1996,22(5):359-362.
[22]Tuan TL,Song A,Chang S,et al.In vitro fibroplasia:matrix contraction,cell growth,and collagen production of fibroblasts cultured in fibrin gels[J].Exp Cell Res,1996,223(1):127-134.
[23]宋述强,程天民,主编.创面愈合与组织修复的生物学过程[M].济南:山东科学技术出版社,1998.7-27.
[24]张敏,刘芳,田蕾,等.锤头状核酶调控CD95介导小鼠皮肤成纤维细胞凋亡[J].中华器官移植杂志,2005,26(2):75-77.
[25]汪进益,张宗明(指导老师).氧自由基对HL-7702人肝细胞钙离子通道的影响[D].上海:同济大学医学院,2004.24-25.
[26]汪进益,李菊香(指导老师).氧化应激对血管内皮细胞ADMA的影响及卡托普利和尼莫地平的作用[D].南昌:南昌大学医学院,2002.10-11.
[27]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社,2003.3-10.
[28]Arakawa M,Hatamochi A,Takeda K,et al.Increased collagen synthesis accompanying elevated m-RNA levels in cultured Werner's syndrome fibroblasts[J].J Invest Dermatol,1990,94(2):187-190.
[29]Friedman DW,Boyd CD,Mackenzie JW,et al.Regulation of collagen gene expression in keloids and hypertrophic scars[J].J Surg Res,1993,55(2):214-222.
[30]黄勇,任林森,岑瑛.瘢痕成纤维细胞培养及其生物学行为的实验研究[J].中国修复重建外科杂志,1998,12(6):332-335.
[31]章静波,主编.组织和细胞培养技术[M].北京:人民卫生出版社,2002.83-84.
[32]Min L J,Cui TX,Yahata Y,et al.Regulation of collagen synthesis in mouse skin fibroblasts by distinct angiotensin Ⅱ receptor subtypes[J].Endocrinology,2004,145(1):253-260.
[33]李峰,吴军正,刘斌,等.动物实验用脱毛剂配方的改进[J].实用口腔医学杂志,1998,14(4):298-299.
[34]韩军涛,陈璧,刘淑娟,等.正常人皮肤成纤维细胞不同培养条件下的生物学特性[J].第四军医大学学报,2000,21(10):1185-1188.
[35]李海红,周岗,付小兵,等.人皮肤成纤维细胞的培养和鉴定[J].中国危重病急救医学,2005,17(21:89-91.
[36]Choi YH,Stamm C,Hammer PE,et al.Cardiac conduction through engineered tissue[J].Am J Pathol,2006,169(1):72-85.
[37]Camelliti P,Green CR,LeGrice I,et al.Fibroblast network in rabbit sinoatrial node:structural and functional identification of homogeneous and heterogeneous cell coupling[J].Circ Res,2004,94(6):828-835.
[38]Munoz-Elias G,Woodbury D,Black IB.Marrow stromal cells,mitosis,and neuronal differentiation:stem cell and precursor functions[J].Stem Cells,2003,21(4):437-448.
[39]Bencsics C,Wachtel SR,Milstien S,et al.Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts[J].J Neurosci,1996,16(14):4449-4456.
[40]汪进益,范慧敏,刘中民.生肌调节因子MyoD、间隙连接蛋白Cx43和分子性心肌成形术[J].同济大学学报(医学版),2006,27(Suppl):5-8.
[41]卢新政,黄峻.心肌成形术的进展[J].中国循环杂志,2002,17(5):399-400.
[42]Krueger GG.Fibroblasts and dermal gene therapy:a minireview[J].Hum Gene Ther,2000,11(16):2289-2296.
[43]陈勇,陈玉祥,龙志高,等.皮肤成纤维细胞体外培养的安全性实验研究[J].中国医师杂志,2002,(11):1176-1179.
[44]Veelken H,Jesuiter H,Mackensen A,et al.Primary fibroblasts from human adults as target cells for ex vivo transfection and gene therapy[J].Hum Gene Ther,1994,5(10):1203-1210.
[45]Roth DA,Tawa NE Jr,O'Brien JM,et al.Nonviral transfer of the gene encoding coagulation factor Ⅷ in patients with severe hemophilia A[J].N Engl J Med,2001,344(23):1735-1742.
[46]Kang WK,Park C,Yoon HL,et al.Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts:outcome of a phase I study[J].Hum Gene Ther,2001,12(6):671-684.
[47]张明,侯蓉,郑鸿培,等.大熊猫皮肤成纤维细胞系的建立和冷冻保存[J].动物学杂志,2005,40(5):61-67.
[48]杨志明,主编.组织工程学[M].北京:化学工业出版社,2002.155-158.
[49]赵智明,蔡辉.心肌成纤维细胞的来源、特征及意义[J].中国微循环,2006,10(3):230-231.
[50]Wildemann B,Schmidmaier G,Ordel S,et al.Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-betal:comparison of two proliferation markers,PCNA and BrdU[J].J Biomed Mater Res B Appl Biomater,2003,65(1):150-156.
[51]Gratzner HG.Monoclonal antibody to 5-bromo-and 5-iododeoxyuridine:A new reagent for detection of DNA replication[J].Science,1982,218(4571):474-475.
[52]Nakamura S,Takeda Y,Kanno M,et al.Application of bromodeoxyuridine(BrdU)and anti-BrdU monoclonal antibody for the in vivo analysis of proliferative characteristics of human leukemia cells in bone marrows[J].Oncology,1991,48(4):285-289.
[53]罗超权,主编.基因诊断与基因治疗进展[M].郑州:河南医科大学出版社,1999.193-197.
[54]陈晴,段德义,杨慧,等.携带酪氨酸羟化酶基因的质粒和逆转录病毒在大鼠成纤维细胞和脑胶质细胞中表达效率的比较[J].解剖学报,2005,36(1):76-80.
[55]Dumcius A,Chekanov V,Vysockas V.Current status of cardiomyoplasty as surgical alternative for end-stage heart failure[J].Medicina(Kaunas),2003,39(9):815-822.
[56]Ludolph DC,Konieczny SF.Transcription factor families:muscling in on the myogenic program[J].FASEB J,1995,9(15):1595-1604.
[57]Smythe GM,Grounds MD.Absence of MyoD increases donor myoblast migration into host muscle[J].Exp Cell Res,2001,267(2):267-274.
[58]Polesskaya A,Rudnicki MA.A MyoD-dependent differentiation checkpoint:ensuring genome integrity[J].Dev Cell,2002,3(6):757-758.
[59]Dhein S,Polontchouk L,Salameh A,et al.Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40[J].Biol Cell,2002,94(7-8):409-422.
[60]Gros DB,Jongsma HJ.Connexins in mammalian heart function[J].Bioessays,1996,18(9):719-730.
[61]徐振平,郭志坤.心脏间隙连接研究进展[J].解剖科学进展,2001,7(3):274-276.
[62]Verheule S,van Kempen MJ,te Welscher PH,et al.Characterization of gap junction channels in adult rabbit atrial and ventricular myocardium[J].Circ Res,1997,80(5):673-681.
[63]Hossain MZ,Boynton AL.Regulation of Cx43 gap junctions:the gatekeeper and the password[J].Sci STKE,2000,2000(54):PE1.
[64]Pawel L,Jennifer M,Bostjan K,et al.Methods for high-throughput protein expression,purification and structure determination adapted for structural genomics.Australian Biochemist,2004,35(2):43-46.
[65]范慧敏,李阳,刘中民.人真核表达的质粒载体pLenti6/V5-DEST-Cx43的构建及鉴定[J].中华胸心血管外科杂志,2006,22(2):130-132.
[66]金冬雁,黎孟枫,编译.分子克隆实验指南[M].北京:科学技术出版社,1992.1-395.
[67]Follenzi A,Ailles LE,Bakovic S,et al.Gene transfer by tentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences[J].Nat Genet,2000,25(2):217-222.
[68]Fleming J,Ginn SL,Weinberger RP,et al.Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons[J].Hum Gene Yher,2001,12(1):77-86.
[69]秦瑞峰,顾晓明,陈金武等.鼠肌肉转录调节因子MyoD基因真核表达载体的构建[J].中国修复重建科杂志,2001,15(5):257-260.
[70]季国忠,张发明,翟惠虹,等.Smad4基因RNAi慢病毒载体的构建与鉴定[J].第四军医大学学报,2006,27(7):600-602.
[71]von Harsdorf R,Poole-Wilson PA,Dietz R.Regenerative capacity of the myocardium:implications for treatment of heart failure[J].Lancet,2004,363(9417):1306-1313.
[72]Murry CE,Kay MA,Bartosek T,et al.Muscle differentiation during repair of myocardial necrosis in rats via gene transfer with MyoD[J].J Clin Invest,1996,98(10):2209-2217.
[73]邹仲敏,程天民,罗成基,等.肌形成及其基因调控的研究进展[J].中国科学基金,2000,14(3):137-142.
[74]Chen JC,Goldhamer DJ.Transcriptional mechanisms regulating MyoD expression in the mouse[J].Cell Tissue Res,1999,296(1):213-219.
[75]Sabourin LA,Rudnicki MA.The molecular regulation of myogenesis[J].Clin Genet,2000,57(1):16-25.
[76]Shore L,McLean P,Gilmour SK,et al.Polyamines regulate gap junction communication in connexin 43-expressing cells[J].Biochem J,2001,357(Pt 2):489-495.
[77]Jongsma H J,Wilders R.Gap junctions in cardiovascular disease[J].Circ Res,2000,86(12):1193-1197.
[78]汪进益,范慧敏,刘中民.心肌细胞Cx43间隙连接半通道活动的研究现状[J].中国分子心脏病学杂志,2006,6(1):47-49.
[79]Chedrawy EG,Wang JS,Nguyen DM,et al.Incorporation and integration of implanted myogenic and stem cells into native myocardial fibers:anatomic basis for functional improvements[J].J Thorac Cardiovasc Surg,2002,124(3):584-590.
[80]Min JJ,Gambhir SS.Gene therapy progress and prospects:noninvasive imaging of gene therapy in living subjects[J].Gene Ther,2004,11(2):115-125.
[81]Blesch A.Lentiviral and MLV based retroviral vectors for ex vivo and in vivo gene transfer [J].Methods,2004,33(2):164-172.
[82]Naldini L,Blomer U,Gallay P,et al.In vivo gene delivery and stable transduction of nondividing ceils by a lentiviral vector[J].Science,1996,272(5259):263-267.
[83]Buchschacher GL Jr,Wong-Staal F.Development of lentiviral vectors for gene therapy for human diseases[J].Blood,2000,95(8):2499-2504.
[84]Nishitsuji H,Ikeda T,Miyoshi H,et al.Expression of small hairpin RNA by lentivirus-based vector confers efficient and stable gene-suppression of HIV-1 on human cells including primary non-dividing cells[J].Microbes Infect,2004,6(1):76-85.
[85]Singer O,Marr RA,Rockenstein E,et al.Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model[J].Nat Neurosci,2005,8(10):1343-1349.
[86]Wiznerowicz M,Trono D.Conditional suppression of cellular genes:lentivirus vector-mediated drug-inducible RNA interference[J].J Virol,2003,77(16):8957-8961.
[87]Hui EK,Yap EM,An DS,et al.Inhibition of influenza virus matrix(M1)protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA[J].J Gen Virol,2004,85(Pt7):1877-1884.
[88]Solaiman F,Zink MA,Xu G,et al.Modular retro-vectors for transgenic and therapeutic use [J].Mol Reprod Dev,2000,56(2Suppl):309-315.
[89]Stewart SA,Dykxhoorn DM,Palliser D,et al.Lentivirus-delivered stable gene silencing by RNAi in primary cells[J].RNA,2003,9(4):493-501.
[90]Yant SR,Ehrhardt A,Mikkelsen JG,et al.Transposition from a gutless adeno-transposon vector stabilizes transgene expression in vivo[J].Nat Biotechnol,2002,20(10):999-1005.
[91]McCormick F.Cancer gene therapy:fringe or cutting edge?[J].Nat Rev Cancer,2001,1(2):130-141.
[92]Bank A.Hematopoietic stem cell gene therapy:selecting only the best[J].J Clin Invest,2003,112(10):1478-1480.
[93]Lois C,Hong EJ,Pease S,et al.Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors[J].Science,2002,295(5556):868-872.
[94]May C,Rivella S,Callegari J,et al.Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin[J].Nature,2000,406(6791):82-86
[95]刘宏伟,盖鲁粤.基因治疗联合干细胞移植修复坏死心肌[J].中国心血管病研究杂志,2004,2(12):982-985.
[96]Rudy Y.The ionic mechanisms of conduction in cardiac tissue[J].J Electrocardiol,2001,34(Suppl):65-68.
[97]Anderson C,Catoe H,Werner R.MIR-206 regulates connexin43 expression during skeletal muscle development[J].Nucleic Acids Res,2006,34(20):5863-5871.
[98]Sambrook J,Fritsch EF,Maniatis T.Molecular cloning.A laboratory manual[M].2nd ed.New York:Cold Spring Harbor Laboratory Press,1989.1015-1020.
[99]顾晓明,毛天球(指导老师).MyoD诱导成纤维细胞分化为肌细胞及肌肉重建的实验研究[D].西安:中国人民解放军第四军医大学,2002.52-55.
[100]F.奥斯伯,RE.金斯顿,JG.塞德曼,等主编.精编分子生物学实验指南[M].北京:科学出版社,1999.332-338.
[101]de Feijter AW,Matesic DF,Ruch RJ,et al.Localization and function of the connexin 43gap-junction protein in normal and various oncogene-expressing rat liver epithelial cells[J].Mol Carcinog,1996,16(4):203-212.
[102]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社, 2003.92-110.
[103]曹翠丽,阎蕴力,马常升,等.大鼠神经干细胞体外生长特性[J].解剖学杂志,2004,27(6):634-638.
[104]Hermens WT,Verhaagen J.Viral vectors,tools for gene transfer in the nervous system[J].Prog Neurobiol,1998,55(4):399-432.
[105]张鹏,陈世益.成肌细胞在肌肉骨骼系统疾病基因治疗中的应用研究进展[J].中国运动医学杂志,2003,22(5):483-486.
[106]杨志明.干细胞、组织工程与再生医学[J].中国修复重建外科杂志,2006,20(2):95-97.
[107]Doering LC.Nervous system modification by transplants and gene transfer[J].Bioessays,1994,16(11):825-831.
[108]李秀兰,张杨,师宜健,等.体外诱导成纤维细胞成骨活性表达的研究[J].中国修复重建外科杂志,2006,20(2):107-111.
[109]Capetanaki Y,Milner DJ,Weitzer G.Desmin in muscle formation and maintenance:knockouts and consequences[J].Cell Struct Funct,1997,22(1):103-116.
[110]Hu B,Wu Z,Phan SH.Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression[J].Am J Respir Cell Mol Biol,2003,29(3Pt1):397-404.
[111]Peters NS.New insights into myocardial arrhythmogenesis:distribution of gap-junctional coupling in normal,ischaemic and hypertrophied human hearts[J].Clin Sci(Lond),1996,90(6):447-452.
[112]van Rijen HV,van Veen TA,Gros D,et al.Connexins and cardiac arrhythmias[J].Adv Cardiol,2006,42:150-160.
[113]汪渊,张素梅,王雪,等.克隆化基因的真核细胞转染[J].安徽医科大学学报,2003,38(5):409-411.
[114]Garfinkel LI,Periasamy M,Nadal-Ginard B.Cloning and characterization of cDNA sequences corresponding to myosin light chains 1,2,and 3,troponin-C,troponin-T,alpha-tropomyosin,and alpha-actin[J].J Biol Chem,1982,257(18):11078-11086.
[115]Buckingham ME,Carvatti M,Minty A,et al.Skeletal muscle myogenesis:the expression of actin and myosin mRNAs[J].Adv Exp Meal Biol,1982,158:331-347.
[116]Rubart M,Pasumarthi KB,Nakajima H,et al.Physiological coupling of donor and host cardiomyocytes after cellular transplantation[J].Circ Res,2003,92(11):1217-1224.
[117]Goessler UR,Riedel K,Hormann K,et al.Perspectives of gene therapy in stem cell tissue engineering[J].Cells Tissues Organs,2006,183(4):169-179.
[118]Boersma E,Mercado N,Poldermans D,et al.Acute myocardial infarction[J].Lancet,2003,361(9360):847-858.
[119]Zammaretti P,Jaconi M.Cardiac tissue engineering:regeneration of the wounded heart[J].Curr Opin Biotechnol,2004,15(5):430-434.
[120]施新道,主编.心血管疾病动物模型.现代医学实验动物学[M].北京:人民卫生出版社,2001.461-472.
[121]Dowell JD,Rubart M,Pasumarthi KB,et al.Myocyte and myogenic stem cell transplantation in the heart[J].Cardiovasc Res,2003,58(2):336-350.
[122]周文武,胡建国,杨进福,等.血管内皮细胞生长因子基因转染骨髓间充质干细胞后心肌移植对促进心肌缺血大鼠心功能恢复的效果评价[J].中国临床康复,2006,10(5):42-45.
[123]张润峰,王继生.建立大鼠心肌梗死模型的若干问题探讨[J].山西医科大学学报,2004,35(1):13-51.
[124]Dourado PM,Tsutsui JM,Mathias W Jr,et al.Evaluation of stunned and infarcted canine myocardium by real time myocardial contrast echocardiography[J].Braz J Med Biol Res,2003,36(11):1501-1509.
[125]周文武,林玲,陈军,等.冠脉结扎法制做大鼠心肌缺血模型[J].中国实验动物学报,2004,12(4):226-230.
[126]汪进益,范慧敏,刘中民.适用于Langendorff离体心脏灌流大鼠心肌梗死动物模型的建立[J].中国比较医学杂志(原名:中国实验动物学杂志),2007,17(1):22-25.
[127]杨建业,张迎春,王明江,等.大鼠左冠状动脉不同结扎时间对心肌梗死面积及心功能的影响[J].郧阳医学院学报,2006,25(2):74-77.
[128]吕铁伟,田杰,江德勤,等.急性心肌梗塞动物模型的建立[J].中国比较医学杂志(原名:中国实验动物学杂志),2004,14(6):166-169.
[129]刘彤,许纲,李广平,等.Langendorff灌流的离体兔心房颤动模型的建立[J].中华实验外科杂志,2004,21(11):1392-1393.
[130]Sharoni R,Olivson A,Chandra M,et al.A 31P NMR study of preconditioned isolated perfused rat heart exposed to intermittent ischemia[J].Magn Resort Med,1996,36(1): 66-71.
[131]Sutherland FJ,Shattock M J,Baker KE,et al.Mouse isolated perfused heart:characteristics and cautions[J].Clin Exp Pharmacol Physiol,2003,30(I1):867-878.
[132]郭磊,吴延庆,曹原,等。氟伐他汀对兔心肌梗死再灌注血清白细胞介素-8及梗死面积的影响[J].临床心血管病杂志,2006,22(4):212-214.
[133]钱远宇,孟庆义,王志忠,等.亚低温疗法减少家兔再灌注急性心肌梗死范围的实验研究[J].中国危重病急救医学,2004,16:129-132.
[134]Ninomiya M,Koyama H,Miyata T,et al.Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model[J].Gene Ther,2003,10(14):1152-1160.
[135]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社,2003.66-72.
[136]Orlic D,Kajstura J,Chimenti S,et al.Bone marrow cells regenerate infarcted myocardium [J].Nature,2001,410(6829):701-705.
[137]尹倪,陈胜喜,罗万俊,等.冠状动脉前降支结扎法制作大鼠急性心肌梗死模型[J].中国医师杂志,2006,8(9):1193-1195.
[138]Lutgens E,Daemen MJ,de Muinck ED,et al.Chronic myocardial infarction in the mouse:cardiac structural and functional changes[J].Cardiovasc Res,1999,41(3):586-593.
[139]Pfeffer MA,Pfeffer JM,Fishbein MC,et al.Myocardial infarct size and ventricular function in rats[J].Circ Res,1979,44(4):503-512.
[140]Moainie SL,Gorman JH,Guy TS,et al.An ovine model of postinfarction dilated cardiomyopathy[J].Ann Thorac Surg,2002,74(3):753-760.
[141]Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages[J].J Thorac Cardiovasc Surg,2000,120(5):999-1005.
[142]苏静怡,李澈,苏哲坦,主编.心脏:从基础到临床[M].北京医科大学,中国协和医科大学联合出版社,1998.492-502.
[143]Sakakibara Y,Tambara K,Lu F,et al.Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction[J].Ann Thorac Surg,2002,74(1):25-30.
[144]Nadal-Ginard B,Kajstura J,Leri A,et al.Myocyte death,growth,and regeneration in cardiac hypertrophy and failure[J].Circ Res,2003,92(2):139-150.
[145]Park JM,Choe YH,Chang S,et al.Usefulness of multidetector-row CT in the evaluation of reperfused myocardial infarction in a rabbit model[J].Korean J Radiol,2004,5(1):19-24.
[146]钮伟真,叶刚,刘萍,等.介绍一套小动物离体灌流心脏心电信号研究设备[J].中国心脏起搏与心电生理杂志,2000,14(2):124-126.
[147]Yamamoto S,Matsumoto N,Kanazawa M,et al.Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts[J].Circulation,2005,111(3):302-309.
[148]许兰文,乔伟伟,陈绍亮,等.离体灌流心动物模型的制备和应用[J].上海实验动物科学,2002,22(2):112-114.
[149]Curtis MJ,Macleod BA,Tabrizchi R,et al.An improved perfusion apparatus for small animal hearts[J].J Pharmacol Methods,1986,15(1):87-94.
[150]Degabriele NM,Griesenbach U,Sato K,et al.Critical appraisal of the mouse model of myocardial infarction[J].Exp Physiol,2004,89(4):497-505.
[151]张冬颖,罗羽慧,杨辉,等.冠状动脉结扎与腹主动脉缩窄所致慢性心力衰竭大鼠模型比较[J].中国微循环,2005,9(3):171-174.
[152]刘超,赵文增,罗鸿.犬急性心肌梗死模型的改进[J].重庆医学,2006,35(9):823-825.
[153]张润峰,魏毅东,张晓刚,等.提高大鼠心肌梗死模型成功率的方法研究[J].同济大学学报(医学版),2005,26:67-69.
[154]Spadaro J,Fishbein MC,Hare C,et al.Characterization of myocardial infarcts in the rat[J].Arch Pathol Lab Med,1980,104(4):179-183.
[155]刘元生,陈运贞.慢性心肌梗塞大鼠实验模型[J].重庆医科大学学报,2002,27(2):153-155.
[156]王淑侠,兰小莉,王吉文,等.大鼠心肌缺血/再灌注损伤模型的改进与评价[J].解剖科学进展,2000,6(4):371-373.
[157]Struthers AD.Pathophysiology of heart failure following myocardial infarction[J].Heart,2005,91(Suppl 2):14-16.
[158]Tiyyagura SR,Pinney SP.Left ventricular remodeling after myocardial infarction:past,present,and future[J].Mt Sinai J Med,2006,73(6):840-851.
[159]Qian H,Yang Y,Huang J,et al.Cellular cardiomyoplasty by catheter-based infusion of stem cells in clinical settings[J].Transpl Immunol,2006,16(3-4):135-147.
[160]Pallante BA,Edelberg JM.Cell sources for cardiac regeneration—which cells and why[J].Am Heart Hosp J,2006,4(2):95-97.
[161]吴国选,伍津津,朱堂友,等.BrdU单抗免疫组化法观察人工皮肤种子细胞生长[J].实用医药杂志,2006,23(1):72-74.
[162]金艳,曹克将(指导老师).骨髓间充质干细胞心肌分化过程中电生理特性及其心肌移植致心律失常机制的研究[D].南京:南京医科大学,2005.134-135.
[163]朱洪生,黄日太,连锋,等.骨髓间质干细胞移植对香猪急性心肌梗死后心肌结构和心功能的影响[J].中国胸心血管外科临床杂志,2004,11(2):112-115.
[164]吴士礼,包宗明,史晓俊,等.急性冠脉综合征患者血浆脑钠素检测及其意义[J].中国心血管病研究杂志,2006,4(4):278-280.
[165]Sutton MG,Sharpe N.Left ventricular remodeling after myocardial infarction:pathophysiology and therapy[J].Circulation,2000,101(25):2981-2988.
[166]林肖峰,余细勇,陈一岳.多基因治疗与细胞移植联合治疗心肌梗死的研究进展[J].中国心血管病研究杂志,2004,2(12):994-998.
[167]蒋路平,周胜华,余国龙,等.心肌梗死后不同时间兔自体骨髓基质细胞移植对疗效的影响[J].临床心血管病杂志,2006,22(8):485-489.
[168]Jaeschke H,Smith CW.Mechanisms of neutrophil-induced parenchymal cell injury[J].J Leukoc Biol,1997,61(6):647-653.
[169]Li RK,Mickle DA,Weisel RD,et al.Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury[J].Ann Thorac Surg,2001,72(6):1957-1963.
[170]Tomita S,Mickle DA,Weisel RD,et al.Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation[J].J Thorac Cardiovasc Surg,2002,123(6):1132-1140.
[171]Vulliet PR,Greeley M,Hal loran SM,et al.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J].Lancet,2004,363(9411):783-784.
[172]Kocher AA,Schuster MD,Szabolcs M J,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7(4):430-436.
[173]伟哉,郭国庆.用BrdU标记技术观察大鼠脊髓上胸段灰质细胞的分化发育[J].解 剖学报,2000,31(4):289-291.
[174]Nemoto R,Hattori K,Sasaki A,et al.Estimations of the S phase fraction in situ in transitional cell carcinoma of the renal pelvis and ureter with bromodeoxyuridine labeling [J].Br J Urol,1989,64(4):339-344.
[175]周秀华,田沈.美托洛尔和雷米普利对急性心肌梗死左室重构和血浆脑钠素影响的比较[J].中国现代医学杂志,2006,16(7):1003-1005.
[176]汪进益,范慧敏,刘中民.犬心肌缺血再灌注损伤心电图Ⅱ导联QRS波群演变的观察[J].中国实验动物学报,2007,15(2):15-18.
[177]Berger R,Huelsman M,Strecker K,et al.B-type natriuretic peptide predicts sudden death in patients with chronic heart failure[J].Circulation,2002,105(20):2392-2397.
[178]张劲林,王方正,张澍,等.脑利钠肽对新生大鼠心室肌细胞缝隙连接蛋白Cx43含量的影响[J].中国心脏起搏与心电生理杂志,2005.19(4):295-297.
[179]Yama GH,Yoshida J,Yamamota K,et al.Elavation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricularhypert rophy[J].J Am Coll Cardiol,2004,43:55-60.
[180]Gackowski A,Lsnard R,Golmard JL,et al.Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure[J].Eur Heart J,2004,25(20):1788-1796.
[181]Maisel AS,Krishnaswamy P,Nowak RM,et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J].N Engl J Med,2002,347:161-167.
[182]Martin-Du Pan RC,Ricou F.Use of brain natriuetic peptide(BNP)in the diagnosis and treatment of heart failure[J].Rev Med Suisse Romande,2003,123(2):125-128.
[183]张悟棠,王凤芝,巩书文,等.脑钠素在评价冠心病介入治疗改善心功能中的价值[J].中国药物与临床,2005,11(5):831-833.
[184]孙彦洵,周江,杨晓.小鼠胚胎干细胞体外定向心肌细胞分化的研究[J].中华心血管病杂志,2001,29(10):601-604.
[1]Anversa P,Nadal-Ginard B.Myocyte renewal and ventricular remodeling[J].Nature,2002,415(6868):240-243.
[2]卢新政,黄峻.心肌成形术的进展[J].中国循环杂志,2002,17(5):399-400.
[3]钱海燕,杨跃进.干细胞心肌再生的移植路径研究进展[J].心血管病学进展,2006,27(4):449-453.
[4]Soonpaa MH,Koh GY,Klug MG,et al.Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium[J].Science,1994,264(5155):98-101.
[5]朱洪生,钟竑,卫洪超,等.自体骨骼肌卫星细胞移植治疗急性心肌梗死的实验研究[J].中华医学杂志,2000,80(11):873-875.
[6]崔勇,陆方林,梅举,等.左心室成形术结合骨骼肌成肌细胞移植治疗心肌梗死后心力衰竭[J].第二军医大学学报,2005,26(9):975-978.
[7]Athanasuleas CL,Stanley AW Jr,Buckberg GD,et al.Surgical anterior ventricular endocardial restoration(SAVER)in the dilated remodeled ventricle after anterior myocardial infarction.RESTORE group.Reconstructive Endoventricular Surgery,returning Torsion Original Radius Elliptical Shape to the LV[J].J Am Coll Cardiol,2001,37(5):1199-1209.
[8]黄佐,葛均波.细胞移植治疗心血管疾病研究现状[J].第二军医大学学报,2004,25(9):929-932.
[9]Min JY,Yang Y,Converso KL,et al.Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats[J].J Appl Physiol,2002,92(1):288-296.
[10]Kizana E,Ginn SL,Allen DG,et al.Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling[J].Circulation,2005,111(4):394-398.
[11]Orlic D,Kajstura J,Chimenti S,et al.Bone marrow cells regenerate infarcted myocardium [J].Nature,2001,410(6829):701-705.
[12]Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans[J].Circulation,2002,106(15):1913-1918.
[13]Jain M,DerSimonian H,Brenner DA,et al.Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction[J].Circulation,2001,103(14):1920-1927.
[14]Roell W,Lu Z J,Bloch W,et al.Cellular cardiomyoplasty improves survival after myocardial injury[J].Circulation,2002,105(20):2435-2441.
[15]Li RK,Jia ZQ,Weisel RD,et al.Smooth muscle cell transplantation into myocardial scar tissue improves heart function[J].J Mol Cell Cardiol,1999,31(3):513-522.
[16]Feld Y,Melamed-Frank M,Kehat I,et al.Electrophysiological modulation of cardiomyocytic tissue by transfected fibroblasts expressing potassium channels:a novel strategy to manipulate excitability[J].Circulation,2002,105(4):522-529.
[17]Zuk PA,Zhu M,Mizuno H,et al.Multilineage cells from human adipose tissue:implications for cell-based therapies[J].Tissue Eng,2001,7(2):211-228.
[18]Fuchs E,Tumbar T,Guasch G.Socializing with the neighbors:stem cells and their niche[J].Cell,2004,116(6):769-778.
[19]Potapova I,Plotnikov A,Lu Z,et al.Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers[J].Circ Res,2004,94(7):952-959.
[20]Kamihata H,Matsubara H,Nishiue T,et al.Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts,angiogenic ligands,and cytokines[J].Circulation,2001,104(9):1046-1052.
[21]连锋,朱洪生,郑家豪,等.骨髓间质干细胞体外转化为肌细胞的研究[J].中华实验外科杂志,2002,19(5):454-456.
[22]Orlic D,Kajstura J,Chimenti S,et al.Mobilized bone marrow cells repair the infarcted heart,improving function and survival[J].Proc Natl Acad Sci USA,2001,98(18):10344-10349.
[23]Kocher AA,Schuster MD,Szabolcs MJ,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7(4):430-436.
[24]Vogel G.Harnessing the power of stem cells[J].Science,1999,283(5407):1432-1434.
[25]Murry CE,Soonpaa MH,Reinecke H,et al.Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts[J].Nature,2004,428(6983):664-668.
[26]Balsam LB,Wagers A J,Christensen JL,et al.Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium[J].Nature,2004,428(6983):668-673.
[27]Kajstura J,Rota M,Whang B,et al.Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion[J].Circ Res,2005,96(1):127-137.
[28]Assmus B,Schachinger V,Teupe C,et al.Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction(TOPCARE-AMI)[J].Circulation,2002,106(24):3009-3017.
[29]Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[30]Menasche P,Hagege AA,Scorsin M,et al.Myoblast transplantation for heart failure[J].Lancet,2001,357(9252):279-280.
[31]Menasche P,Hagege AA,Vilquin JT,et al.Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction[J].J Am Coll Cardiol,2003,41(7):1078-1083.
[32]Leobon B,Garcin I,Menasche P,et al.Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host[J].Proc Natl Acad Sci USA,2003,100(13):7808-7811.
[33]Hamano K,Nishida M,Hirata K,et al.Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease:clinical trial and preliminary results[J].Jpn Circ J,2001,65(9):845-847.
[34]Schachinger V,Assmus B,Britten MB,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction:final one-year results of the TOPCARE-AMI Trial[J].J Am Coll Cardiol,2004,44(8):1690-1699.
[35]Britten MB,Abolmaali ND,Assmus B,et al.Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction(TOPCARE-AMI):mechanistic insights from serial contrast-enhanced magnetic resonance imaging[J].Circulation,2003,108(18):2212-2218.
[36]Perin EC,Dohmann HF,Borojevic R,et al.Transendocardial,autologous bone marrow cell transplantation for severe,chronic ischemic heart failure[J].Circulation,2003,107(18):2294-2302.
[37]Kuethe F,Richartz BM,Kasper C,et al.Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans[J].Int J Cardiol,2005,100(3):485-491.
[38]Janssens S,Dubois C,Bogaert J,et al.Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction:double-blind,randomised controlled trial[J].Lancet,2006,367(9505):113-121.
[39]蒋文慧,马爱群.骨髓干细胞动员治疗缺血性心脏病研究进展[J].中国循环杂志,2003,83(21):1923-1925.
[40]Suarez de Lezo J,Torres A,Herrera I,et al.Effects of stem-cell mobilization with recombinant human granulocyte colony stimulating factor in patients with percutaneously revascularized acute anterior myocardial infarction[J].Rev Esp Cardiol,2005,58(3):253-261.
[41]Wang Y,Tagil K,Ripa RS,et al.Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms,left ventricular perfusion and function in patients with severe chronic ischemic heart disease[J].Int J Cardiol,2005,100(3):477-483.
[42]李延林,葛均波,钱菊英,等.急诊经冠状动脉自体骨髓单个核细胞移植治疗急性心肌梗死的临床研究(TCTSTAMI)[J].中国介入心脏病学杂志,2005,13(3):142-145.
[43]葛均波,李延林,钱菊英,等.陈旧性前壁心肌梗死患者自体骨髓单个核细胞移植后左室心肌灌注及收缩功能的变化[J].中国介入心脏病学杂志,2004,12(5):261-264.
[44]黄榕羽中,姚康,葛均波,等.经冠状动脉骨髓单个核细胞移植治疗原发性扩张型心肌病的安全性与疗效近期观察[J].中华心血管病杂志,2006,34(2):111-113.
[45]李占全,张明,金元哲,等.粒细胞集落刺激因子动员自体骨髓外周血干细胞移植治疗急性心肌梗死的临床研究[J].中华心血管病杂志,2006,34(2):99-102.
[46]王建安,谢小洁,何红,等.骨髓间质干细胞移植治疗原发性扩张型心肌病的疗效与安全性[J].中华心血管病杂志,2006,34(2):107-110.
[47]窦克非,杨跃进,杨伟宪,等.成体犬骨骼肌成肌细胞移植于急性心肌梗死区的试验研究[J].中华心血管病杂志,2005,33(11):1033-1036.
[48]Rafii S,Lyden D.Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J].Nat Med,2003,9(6):702-712.
[49]Pagani FD,DerSimonian H,Zawadzka A,et al.Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans.Histological analysis of cell survival and differentiation[J].J Am Coll Cardiol,2003,41(5):879-888.
[50]Barbash IM,Chouraqui P,Baron J,et al.Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium:feasibility,cell migration,and body distribution [J]. Circulation, 2003,108(7): 863-868.
[51] Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine [J]. Genes Dev, 2005,19(10): 1129-1155.
[52] Akashi K, Traver D, Zon LI. The complex cartography of stem cell commitment [J]. Cell, 2005,121(2): 160-162.
[53] Conrad C, Huss R. Adult stem cell lines in regenerative medicine and reconstructive surgery [J]. J Surg Res, 2005,124(2): 201-208.
[54] Reinecke H, Zhang M, Bartosek T, et al. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts [J]. Circulation, 1999,100(2): 193-202.
[55] Ge J, Li Y, Qian J, et al. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI) [J]. Heart, 2006,92(12): 1764-1767.
[56] Ciulla MM, Ferrero S, Lazzari L, et al. The translocation of marrow MNCs after experimental myocardial cryoinjury is proportional to the infarcted area [J]. Transfusion, 2004,44(2): 239-244.
[57] Siminiak T, Fiszer D, Jerzykowska O, et al. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial [J]. Eur Heart J, 2005,26(12): 1188-1195.
[58] Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts [J]. Nat Med, 2003,9(9): 1195-1201.
[59] Vicario J, Campos C, Piva J, et al. Transcoronary sinus administration of autologous bone marrow in patients with chronic refractory stable angina Phase 1 [J]. Cardiovasc Radiat Med, 2004, 5(2): 71-76.
[60] Aicher A, Brenner W, Zuhayra M, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling [J]. Circulation, 2003, 107(16): 2134-2139.
[61]王建安.干细胞移植治疗心肌梗死的前景[J].中华急诊医学杂志,2006,15(4):304-305.
[62]Yau TM,Tomita S,Weisel RD,et al.Beneficial effect of autologous cell transplantation on infarcted heart function:comparison between bone marrow stromal cells and heart cells[J].Ann Thorac Surg,2003,75(1):169-176.
[63]Ittrich H,Lange C,Dahnke H,et al.Labeling of mesenchymal stem cells with different superparamagnetic particles of iron oxide and detectability with MRI at 3T[J].Rofo,2005,177(8):1151-1163.
[64]Kang H J,Kim HS,Zhang SY,et al.Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction:the MAGIC cell randomised clinical trial[J].Lancet,2004,363(9411):751-756.
[65]Vulliet PR,Greeley M,Halloran SM,et al.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J].Lancet,2004,363(9411):783-784.
[66]Yoon YS,Park JS,Tkebuchava T,et al.Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction[J].Circulation,2004,109(25):3154-3157.
[67]Rubio D,Garcia-Castro J,Martin MC,et al.Spontaneous human adult stem cell transformation[J].Cancer Res,2005,65(8):3035-3039.
[68]Zhang YM,Hartzell C,Narlow M,et al.Stem cell-derived cardiomyocytes demonstrate arrhythmic potential[J].Circulation,2002,106(10):1294-1299.
[69]Marx J.Cancer research.Mutant stem cells may seed cancer[J].Science,2003,301(5638):1308-1310.
[70]Ii M,Losordo DW.Transplant graft vasculopathy:a dark side of bone marrow stem cells[J]?Circulation,2003,108(25):3056-3058.
[2] Bolognese L, Neskovic AN, Parodi G, et al. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications [J]. Circulation, 2002,106(18): 2351-2357.
[3] Hughes S. Cardiac stem cells [J]. J Pathol, 2002,197(4): 468-478.
[4] Soonpaa MH, Koh GY, Klug MG, et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium [J]. Science, 1994,264(5155): 98-101.
[5] Barile L, Chimenti I, Gaetani R, et al. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration [J]. Nat Clin Pract Cardiovasc Med, 2007, Suppl 1(S1): S9-S14.
[6] Chachques JC, Salanson-Lajos C, Lajos P, et al. Cellular cardiomyoplasty for myocardial regeneration [J]. Asian Cardiovasc Thorac Ann, 2005,13(3): 287-296.
[7] Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes [J]. Circ Res, 2002,91(3): 189-201.
[8] Burashnikov A, Antzelevitch C. Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations [J]. J Cardiovasc Electrophysiol, 2002,13(2): 172-177.
[9] Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up [J]. J Am Coll Cardiol, 2003,42(12): 2063-2069.
[10] Siminiak T, Kalawski R, Fiszer D, et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up [J]. Am Heart J, 2004, 148(3): 531-537.
[11] Bonaros N, Bernecker O, Ott H, et al. Cell- and gene therapy for ischemic heart disease [J]. Minerva Cardioangiol, 2005, 53(4): 265-273.
[12] Dedkov EI, Kostrominova TY, Borisov AB, et al. MyoD and myogenin protein expression in skeletal muscles of senile rats [J]. Cell Tissue Res, 2003, 311(3): 401-416.
[13] Suzuki K, Brand NJ, Allen S, et al. Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart [J]. J Thorac Cardiovasc Surg, 2001, 122(4): 759-766.
[14]范慧敏,汪进益,刘中民,等.Cx43转基因自体成肌细胞移植对犬急性心肌梗死后心肌结构和心功能的影响[J].中华实验外科杂志,2006,23(11):1328-1330.
[15]Etzion S,Barbash IM,Feinberg MS,et al.Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo:an unlimited source of cells for myocardial repair[J].Circulation,2002,106(12 Suppl 1):I125-130.
[16]汪进益,范慧敏,刘中民,等.大鼠皮肤成纤维细胞MyoD cDNA转染后的形态变化[J].同济大学学报(医学版),2007,28(1):6-9.
[17]Kizana E,Ginn SL,Allen DG,et al.Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling[J].Circulation,2005,111(4):394-398.
[18]崔磊,尹烁,邓辰亮,等.软骨形态发生蛋白1诱导真皮成纤维细胞向软骨细胞表型分化的影响因素[J].中华医学杂志,2005,85(33):2331-2337.
[19]唐佩弦.干细胞基础研究的新进展[J].基础医学与临床,2006,6(1):1-11.
[20]Marusic A,Katavic V,Grcevic D.Genetic variability of new bone induction in mice[J].Bone,1999,25(1):25-32.
[21]Moulin V,Castilloux G,Jean A,et al.In vitro models to study wound healing fibroblasts[J].Burns,1996,22(5):359-362.
[22]Tuan TL,Song A,Chang S,et al.In vitro fibroplasia:matrix contraction,cell growth,and collagen production of fibroblasts cultured in fibrin gels[J].Exp Cell Res,1996,223(1):127-134.
[23]宋述强,程天民,主编.创面愈合与组织修复的生物学过程[M].济南:山东科学技术出版社,1998.7-27.
[24]张敏,刘芳,田蕾,等.锤头状核酶调控CD95介导小鼠皮肤成纤维细胞凋亡[J].中华器官移植杂志,2005,26(2):75-77.
[25]汪进益,张宗明(指导老师).氧自由基对HL-7702人肝细胞钙离子通道的影响[D].上海:同济大学医学院,2004.24-25.
[26]汪进益,李菊香(指导老师).氧化应激对血管内皮细胞ADMA的影响及卡托普利和尼莫地平的作用[D].南昌:南昌大学医学院,2002.10-11.
[27]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社,2003.3-10.
[28]Arakawa M,Hatamochi A,Takeda K,et al.Increased collagen synthesis accompanying elevated m-RNA levels in cultured Werner's syndrome fibroblasts[J].J Invest Dermatol,1990,94(2):187-190.
[29]Friedman DW,Boyd CD,Mackenzie JW,et al.Regulation of collagen gene expression in keloids and hypertrophic scars[J].J Surg Res,1993,55(2):214-222.
[30]黄勇,任林森,岑瑛.瘢痕成纤维细胞培养及其生物学行为的实验研究[J].中国修复重建外科杂志,1998,12(6):332-335.
[31]章静波,主编.组织和细胞培养技术[M].北京:人民卫生出版社,2002.83-84.
[32]Min L J,Cui TX,Yahata Y,et al.Regulation of collagen synthesis in mouse skin fibroblasts by distinct angiotensin Ⅱ receptor subtypes[J].Endocrinology,2004,145(1):253-260.
[33]李峰,吴军正,刘斌,等.动物实验用脱毛剂配方的改进[J].实用口腔医学杂志,1998,14(4):298-299.
[34]韩军涛,陈璧,刘淑娟,等.正常人皮肤成纤维细胞不同培养条件下的生物学特性[J].第四军医大学学报,2000,21(10):1185-1188.
[35]李海红,周岗,付小兵,等.人皮肤成纤维细胞的培养和鉴定[J].中国危重病急救医学,2005,17(21:89-91.
[36]Choi YH,Stamm C,Hammer PE,et al.Cardiac conduction through engineered tissue[J].Am J Pathol,2006,169(1):72-85.
[37]Camelliti P,Green CR,LeGrice I,et al.Fibroblast network in rabbit sinoatrial node:structural and functional identification of homogeneous and heterogeneous cell coupling[J].Circ Res,2004,94(6):828-835.
[38]Munoz-Elias G,Woodbury D,Black IB.Marrow stromal cells,mitosis,and neuronal differentiation:stem cell and precursor functions[J].Stem Cells,2003,21(4):437-448.
[39]Bencsics C,Wachtel SR,Milstien S,et al.Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts[J].J Neurosci,1996,16(14):4449-4456.
[40]汪进益,范慧敏,刘中民.生肌调节因子MyoD、间隙连接蛋白Cx43和分子性心肌成形术[J].同济大学学报(医学版),2006,27(Suppl):5-8.
[41]卢新政,黄峻.心肌成形术的进展[J].中国循环杂志,2002,17(5):399-400.
[42]Krueger GG.Fibroblasts and dermal gene therapy:a minireview[J].Hum Gene Ther,2000,11(16):2289-2296.
[43]陈勇,陈玉祥,龙志高,等.皮肤成纤维细胞体外培养的安全性实验研究[J].中国医师杂志,2002,(11):1176-1179.
[44]Veelken H,Jesuiter H,Mackensen A,et al.Primary fibroblasts from human adults as target cells for ex vivo transfection and gene therapy[J].Hum Gene Ther,1994,5(10):1203-1210.
[45]Roth DA,Tawa NE Jr,O'Brien JM,et al.Nonviral transfer of the gene encoding coagulation factor Ⅷ in patients with severe hemophilia A[J].N Engl J Med,2001,344(23):1735-1742.
[46]Kang WK,Park C,Yoon HL,et al.Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts:outcome of a phase I study[J].Hum Gene Ther,2001,12(6):671-684.
[47]张明,侯蓉,郑鸿培,等.大熊猫皮肤成纤维细胞系的建立和冷冻保存[J].动物学杂志,2005,40(5):61-67.
[48]杨志明,主编.组织工程学[M].北京:化学工业出版社,2002.155-158.
[49]赵智明,蔡辉.心肌成纤维细胞的来源、特征及意义[J].中国微循环,2006,10(3):230-231.
[50]Wildemann B,Schmidmaier G,Ordel S,et al.Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-betal:comparison of two proliferation markers,PCNA and BrdU[J].J Biomed Mater Res B Appl Biomater,2003,65(1):150-156.
[51]Gratzner HG.Monoclonal antibody to 5-bromo-and 5-iododeoxyuridine:A new reagent for detection of DNA replication[J].Science,1982,218(4571):474-475.
[52]Nakamura S,Takeda Y,Kanno M,et al.Application of bromodeoxyuridine(BrdU)and anti-BrdU monoclonal antibody for the in vivo analysis of proliferative characteristics of human leukemia cells in bone marrows[J].Oncology,1991,48(4):285-289.
[53]罗超权,主编.基因诊断与基因治疗进展[M].郑州:河南医科大学出版社,1999.193-197.
[54]陈晴,段德义,杨慧,等.携带酪氨酸羟化酶基因的质粒和逆转录病毒在大鼠成纤维细胞和脑胶质细胞中表达效率的比较[J].解剖学报,2005,36(1):76-80.
[55]Dumcius A,Chekanov V,Vysockas V.Current status of cardiomyoplasty as surgical alternative for end-stage heart failure[J].Medicina(Kaunas),2003,39(9):815-822.
[56]Ludolph DC,Konieczny SF.Transcription factor families:muscling in on the myogenic program[J].FASEB J,1995,9(15):1595-1604.
[57]Smythe GM,Grounds MD.Absence of MyoD increases donor myoblast migration into host muscle[J].Exp Cell Res,2001,267(2):267-274.
[58]Polesskaya A,Rudnicki MA.A MyoD-dependent differentiation checkpoint:ensuring genome integrity[J].Dev Cell,2002,3(6):757-758.
[59]Dhein S,Polontchouk L,Salameh A,et al.Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40[J].Biol Cell,2002,94(7-8):409-422.
[60]Gros DB,Jongsma HJ.Connexins in mammalian heart function[J].Bioessays,1996,18(9):719-730.
[61]徐振平,郭志坤.心脏间隙连接研究进展[J].解剖科学进展,2001,7(3):274-276.
[62]Verheule S,van Kempen MJ,te Welscher PH,et al.Characterization of gap junction channels in adult rabbit atrial and ventricular myocardium[J].Circ Res,1997,80(5):673-681.
[63]Hossain MZ,Boynton AL.Regulation of Cx43 gap junctions:the gatekeeper and the password[J].Sci STKE,2000,2000(54):PE1.
[64]Pawel L,Jennifer M,Bostjan K,et al.Methods for high-throughput protein expression,purification and structure determination adapted for structural genomics.Australian Biochemist,2004,35(2):43-46.
[65]范慧敏,李阳,刘中民.人真核表达的质粒载体pLenti6/V5-DEST-Cx43的构建及鉴定[J].中华胸心血管外科杂志,2006,22(2):130-132.
[66]金冬雁,黎孟枫,编译.分子克隆实验指南[M].北京:科学技术出版社,1992.1-395.
[67]Follenzi A,Ailles LE,Bakovic S,et al.Gene transfer by tentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences[J].Nat Genet,2000,25(2):217-222.
[68]Fleming J,Ginn SL,Weinberger RP,et al.Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons[J].Hum Gene Yher,2001,12(1):77-86.
[69]秦瑞峰,顾晓明,陈金武等.鼠肌肉转录调节因子MyoD基因真核表达载体的构建[J].中国修复重建科杂志,2001,15(5):257-260.
[70]季国忠,张发明,翟惠虹,等.Smad4基因RNAi慢病毒载体的构建与鉴定[J].第四军医大学学报,2006,27(7):600-602.
[71]von Harsdorf R,Poole-Wilson PA,Dietz R.Regenerative capacity of the myocardium:implications for treatment of heart failure[J].Lancet,2004,363(9417):1306-1313.
[72]Murry CE,Kay MA,Bartosek T,et al.Muscle differentiation during repair of myocardial necrosis in rats via gene transfer with MyoD[J].J Clin Invest,1996,98(10):2209-2217.
[73]邹仲敏,程天民,罗成基,等.肌形成及其基因调控的研究进展[J].中国科学基金,2000,14(3):137-142.
[74]Chen JC,Goldhamer DJ.Transcriptional mechanisms regulating MyoD expression in the mouse[J].Cell Tissue Res,1999,296(1):213-219.
[75]Sabourin LA,Rudnicki MA.The molecular regulation of myogenesis[J].Clin Genet,2000,57(1):16-25.
[76]Shore L,McLean P,Gilmour SK,et al.Polyamines regulate gap junction communication in connexin 43-expressing cells[J].Biochem J,2001,357(Pt 2):489-495.
[77]Jongsma H J,Wilders R.Gap junctions in cardiovascular disease[J].Circ Res,2000,86(12):1193-1197.
[78]汪进益,范慧敏,刘中民.心肌细胞Cx43间隙连接半通道活动的研究现状[J].中国分子心脏病学杂志,2006,6(1):47-49.
[79]Chedrawy EG,Wang JS,Nguyen DM,et al.Incorporation and integration of implanted myogenic and stem cells into native myocardial fibers:anatomic basis for functional improvements[J].J Thorac Cardiovasc Surg,2002,124(3):584-590.
[80]Min JJ,Gambhir SS.Gene therapy progress and prospects:noninvasive imaging of gene therapy in living subjects[J].Gene Ther,2004,11(2):115-125.
[81]Blesch A.Lentiviral and MLV based retroviral vectors for ex vivo and in vivo gene transfer [J].Methods,2004,33(2):164-172.
[82]Naldini L,Blomer U,Gallay P,et al.In vivo gene delivery and stable transduction of nondividing ceils by a lentiviral vector[J].Science,1996,272(5259):263-267.
[83]Buchschacher GL Jr,Wong-Staal F.Development of lentiviral vectors for gene therapy for human diseases[J].Blood,2000,95(8):2499-2504.
[84]Nishitsuji H,Ikeda T,Miyoshi H,et al.Expression of small hairpin RNA by lentivirus-based vector confers efficient and stable gene-suppression of HIV-1 on human cells including primary non-dividing cells[J].Microbes Infect,2004,6(1):76-85.
[85]Singer O,Marr RA,Rockenstein E,et al.Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model[J].Nat Neurosci,2005,8(10):1343-1349.
[86]Wiznerowicz M,Trono D.Conditional suppression of cellular genes:lentivirus vector-mediated drug-inducible RNA interference[J].J Virol,2003,77(16):8957-8961.
[87]Hui EK,Yap EM,An DS,et al.Inhibition of influenza virus matrix(M1)protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA[J].J Gen Virol,2004,85(Pt7):1877-1884.
[88]Solaiman F,Zink MA,Xu G,et al.Modular retro-vectors for transgenic and therapeutic use [J].Mol Reprod Dev,2000,56(2Suppl):309-315.
[89]Stewart SA,Dykxhoorn DM,Palliser D,et al.Lentivirus-delivered stable gene silencing by RNAi in primary cells[J].RNA,2003,9(4):493-501.
[90]Yant SR,Ehrhardt A,Mikkelsen JG,et al.Transposition from a gutless adeno-transposon vector stabilizes transgene expression in vivo[J].Nat Biotechnol,2002,20(10):999-1005.
[91]McCormick F.Cancer gene therapy:fringe or cutting edge?[J].Nat Rev Cancer,2001,1(2):130-141.
[92]Bank A.Hematopoietic stem cell gene therapy:selecting only the best[J].J Clin Invest,2003,112(10):1478-1480.
[93]Lois C,Hong EJ,Pease S,et al.Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors[J].Science,2002,295(5556):868-872.
[94]May C,Rivella S,Callegari J,et al.Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin[J].Nature,2000,406(6791):82-86
[95]刘宏伟,盖鲁粤.基因治疗联合干细胞移植修复坏死心肌[J].中国心血管病研究杂志,2004,2(12):982-985.
[96]Rudy Y.The ionic mechanisms of conduction in cardiac tissue[J].J Electrocardiol,2001,34(Suppl):65-68.
[97]Anderson C,Catoe H,Werner R.MIR-206 regulates connexin43 expression during skeletal muscle development[J].Nucleic Acids Res,2006,34(20):5863-5871.
[98]Sambrook J,Fritsch EF,Maniatis T.Molecular cloning.A laboratory manual[M].2nd ed.New York:Cold Spring Harbor Laboratory Press,1989.1015-1020.
[99]顾晓明,毛天球(指导老师).MyoD诱导成纤维细胞分化为肌细胞及肌肉重建的实验研究[D].西安:中国人民解放军第四军医大学,2002.52-55.
[100]F.奥斯伯,RE.金斯顿,JG.塞德曼,等主编.精编分子生物学实验指南[M].北京:科学出版社,1999.332-338.
[101]de Feijter AW,Matesic DF,Ruch RJ,et al.Localization and function of the connexin 43gap-junction protein in normal and various oncogene-expressing rat liver epithelial cells[J].Mol Carcinog,1996,16(4):203-212.
[102]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社, 2003.92-110.
[103]曹翠丽,阎蕴力,马常升,等.大鼠神经干细胞体外生长特性[J].解剖学杂志,2004,27(6):634-638.
[104]Hermens WT,Verhaagen J.Viral vectors,tools for gene transfer in the nervous system[J].Prog Neurobiol,1998,55(4):399-432.
[105]张鹏,陈世益.成肌细胞在肌肉骨骼系统疾病基因治疗中的应用研究进展[J].中国运动医学杂志,2003,22(5):483-486.
[106]杨志明.干细胞、组织工程与再生医学[J].中国修复重建外科杂志,2006,20(2):95-97.
[107]Doering LC.Nervous system modification by transplants and gene transfer[J].Bioessays,1994,16(11):825-831.
[108]李秀兰,张杨,师宜健,等.体外诱导成纤维细胞成骨活性表达的研究[J].中国修复重建外科杂志,2006,20(2):107-111.
[109]Capetanaki Y,Milner DJ,Weitzer G.Desmin in muscle formation and maintenance:knockouts and consequences[J].Cell Struct Funct,1997,22(1):103-116.
[110]Hu B,Wu Z,Phan SH.Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression[J].Am J Respir Cell Mol Biol,2003,29(3Pt1):397-404.
[111]Peters NS.New insights into myocardial arrhythmogenesis:distribution of gap-junctional coupling in normal,ischaemic and hypertrophied human hearts[J].Clin Sci(Lond),1996,90(6):447-452.
[112]van Rijen HV,van Veen TA,Gros D,et al.Connexins and cardiac arrhythmias[J].Adv Cardiol,2006,42:150-160.
[113]汪渊,张素梅,王雪,等.克隆化基因的真核细胞转染[J].安徽医科大学学报,2003,38(5):409-411.
[114]Garfinkel LI,Periasamy M,Nadal-Ginard B.Cloning and characterization of cDNA sequences corresponding to myosin light chains 1,2,and 3,troponin-C,troponin-T,alpha-tropomyosin,and alpha-actin[J].J Biol Chem,1982,257(18):11078-11086.
[115]Buckingham ME,Carvatti M,Minty A,et al.Skeletal muscle myogenesis:the expression of actin and myosin mRNAs[J].Adv Exp Meal Biol,1982,158:331-347.
[116]Rubart M,Pasumarthi KB,Nakajima H,et al.Physiological coupling of donor and host cardiomyocytes after cellular transplantation[J].Circ Res,2003,92(11):1217-1224.
[117]Goessler UR,Riedel K,Hormann K,et al.Perspectives of gene therapy in stem cell tissue engineering[J].Cells Tissues Organs,2006,183(4):169-179.
[118]Boersma E,Mercado N,Poldermans D,et al.Acute myocardial infarction[J].Lancet,2003,361(9360):847-858.
[119]Zammaretti P,Jaconi M.Cardiac tissue engineering:regeneration of the wounded heart[J].Curr Opin Biotechnol,2004,15(5):430-434.
[120]施新道,主编.心血管疾病动物模型.现代医学实验动物学[M].北京:人民卫生出版社,2001.461-472.
[121]Dowell JD,Rubart M,Pasumarthi KB,et al.Myocyte and myogenic stem cell transplantation in the heart[J].Cardiovasc Res,2003,58(2):336-350.
[122]周文武,胡建国,杨进福,等.血管内皮细胞生长因子基因转染骨髓间充质干细胞后心肌移植对促进心肌缺血大鼠心功能恢复的效果评价[J].中国临床康复,2006,10(5):42-45.
[123]张润峰,王继生.建立大鼠心肌梗死模型的若干问题探讨[J].山西医科大学学报,2004,35(1):13-51.
[124]Dourado PM,Tsutsui JM,Mathias W Jr,et al.Evaluation of stunned and infarcted canine myocardium by real time myocardial contrast echocardiography[J].Braz J Med Biol Res,2003,36(11):1501-1509.
[125]周文武,林玲,陈军,等.冠脉结扎法制做大鼠心肌缺血模型[J].中国实验动物学报,2004,12(4):226-230.
[126]汪进益,范慧敏,刘中民.适用于Langendorff离体心脏灌流大鼠心肌梗死动物模型的建立[J].中国比较医学杂志(原名:中国实验动物学杂志),2007,17(1):22-25.
[127]杨建业,张迎春,王明江,等.大鼠左冠状动脉不同结扎时间对心肌梗死面积及心功能的影响[J].郧阳医学院学报,2006,25(2):74-77.
[128]吕铁伟,田杰,江德勤,等.急性心肌梗塞动物模型的建立[J].中国比较医学杂志(原名:中国实验动物学杂志),2004,14(6):166-169.
[129]刘彤,许纲,李广平,等.Langendorff灌流的离体兔心房颤动模型的建立[J].中华实验外科杂志,2004,21(11):1392-1393.
[130]Sharoni R,Olivson A,Chandra M,et al.A 31P NMR study of preconditioned isolated perfused rat heart exposed to intermittent ischemia[J].Magn Resort Med,1996,36(1): 66-71.
[131]Sutherland FJ,Shattock M J,Baker KE,et al.Mouse isolated perfused heart:characteristics and cautions[J].Clin Exp Pharmacol Physiol,2003,30(I1):867-878.
[132]郭磊,吴延庆,曹原,等。氟伐他汀对兔心肌梗死再灌注血清白细胞介素-8及梗死面积的影响[J].临床心血管病杂志,2006,22(4):212-214.
[133]钱远宇,孟庆义,王志忠,等.亚低温疗法减少家兔再灌注急性心肌梗死范围的实验研究[J].中国危重病急救医学,2004,16:129-132.
[134]Ninomiya M,Koyama H,Miyata T,et al.Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model[J].Gene Ther,2003,10(14):1152-1160.
[135]蔡文琴,主编.现代实用细胞与分子生物学实验技术[M].北京:人民军医出版社,2003.66-72.
[136]Orlic D,Kajstura J,Chimenti S,et al.Bone marrow cells regenerate infarcted myocardium [J].Nature,2001,410(6829):701-705.
[137]尹倪,陈胜喜,罗万俊,等.冠状动脉前降支结扎法制作大鼠急性心肌梗死模型[J].中国医师杂志,2006,8(9):1193-1195.
[138]Lutgens E,Daemen MJ,de Muinck ED,et al.Chronic myocardial infarction in the mouse:cardiac structural and functional changes[J].Cardiovasc Res,1999,41(3):586-593.
[139]Pfeffer MA,Pfeffer JM,Fishbein MC,et al.Myocardial infarct size and ventricular function in rats[J].Circ Res,1979,44(4):503-512.
[140]Moainie SL,Gorman JH,Guy TS,et al.An ovine model of postinfarction dilated cardiomyopathy[J].Ann Thorac Surg,2002,74(3):753-760.
[141]Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages[J].J Thorac Cardiovasc Surg,2000,120(5):999-1005.
[142]苏静怡,李澈,苏哲坦,主编.心脏:从基础到临床[M].北京医科大学,中国协和医科大学联合出版社,1998.492-502.
[143]Sakakibara Y,Tambara K,Lu F,et al.Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction[J].Ann Thorac Surg,2002,74(1):25-30.
[144]Nadal-Ginard B,Kajstura J,Leri A,et al.Myocyte death,growth,and regeneration in cardiac hypertrophy and failure[J].Circ Res,2003,92(2):139-150.
[145]Park JM,Choe YH,Chang S,et al.Usefulness of multidetector-row CT in the evaluation of reperfused myocardial infarction in a rabbit model[J].Korean J Radiol,2004,5(1):19-24.
[146]钮伟真,叶刚,刘萍,等.介绍一套小动物离体灌流心脏心电信号研究设备[J].中国心脏起搏与心电生理杂志,2000,14(2):124-126.
[147]Yamamoto S,Matsumoto N,Kanazawa M,et al.Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts[J].Circulation,2005,111(3):302-309.
[148]许兰文,乔伟伟,陈绍亮,等.离体灌流心动物模型的制备和应用[J].上海实验动物科学,2002,22(2):112-114.
[149]Curtis MJ,Macleod BA,Tabrizchi R,et al.An improved perfusion apparatus for small animal hearts[J].J Pharmacol Methods,1986,15(1):87-94.
[150]Degabriele NM,Griesenbach U,Sato K,et al.Critical appraisal of the mouse model of myocardial infarction[J].Exp Physiol,2004,89(4):497-505.
[151]张冬颖,罗羽慧,杨辉,等.冠状动脉结扎与腹主动脉缩窄所致慢性心力衰竭大鼠模型比较[J].中国微循环,2005,9(3):171-174.
[152]刘超,赵文增,罗鸿.犬急性心肌梗死模型的改进[J].重庆医学,2006,35(9):823-825.
[153]张润峰,魏毅东,张晓刚,等.提高大鼠心肌梗死模型成功率的方法研究[J].同济大学学报(医学版),2005,26:67-69.
[154]Spadaro J,Fishbein MC,Hare C,et al.Characterization of myocardial infarcts in the rat[J].Arch Pathol Lab Med,1980,104(4):179-183.
[155]刘元生,陈运贞.慢性心肌梗塞大鼠实验模型[J].重庆医科大学学报,2002,27(2):153-155.
[156]王淑侠,兰小莉,王吉文,等.大鼠心肌缺血/再灌注损伤模型的改进与评价[J].解剖科学进展,2000,6(4):371-373.
[157]Struthers AD.Pathophysiology of heart failure following myocardial infarction[J].Heart,2005,91(Suppl 2):14-16.
[158]Tiyyagura SR,Pinney SP.Left ventricular remodeling after myocardial infarction:past,present,and future[J].Mt Sinai J Med,2006,73(6):840-851.
[159]Qian H,Yang Y,Huang J,et al.Cellular cardiomyoplasty by catheter-based infusion of stem cells in clinical settings[J].Transpl Immunol,2006,16(3-4):135-147.
[160]Pallante BA,Edelberg JM.Cell sources for cardiac regeneration—which cells and why[J].Am Heart Hosp J,2006,4(2):95-97.
[161]吴国选,伍津津,朱堂友,等.BrdU单抗免疫组化法观察人工皮肤种子细胞生长[J].实用医药杂志,2006,23(1):72-74.
[162]金艳,曹克将(指导老师).骨髓间充质干细胞心肌分化过程中电生理特性及其心肌移植致心律失常机制的研究[D].南京:南京医科大学,2005.134-135.
[163]朱洪生,黄日太,连锋,等.骨髓间质干细胞移植对香猪急性心肌梗死后心肌结构和心功能的影响[J].中国胸心血管外科临床杂志,2004,11(2):112-115.
[164]吴士礼,包宗明,史晓俊,等.急性冠脉综合征患者血浆脑钠素检测及其意义[J].中国心血管病研究杂志,2006,4(4):278-280.
[165]Sutton MG,Sharpe N.Left ventricular remodeling after myocardial infarction:pathophysiology and therapy[J].Circulation,2000,101(25):2981-2988.
[166]林肖峰,余细勇,陈一岳.多基因治疗与细胞移植联合治疗心肌梗死的研究进展[J].中国心血管病研究杂志,2004,2(12):994-998.
[167]蒋路平,周胜华,余国龙,等.心肌梗死后不同时间兔自体骨髓基质细胞移植对疗效的影响[J].临床心血管病杂志,2006,22(8):485-489.
[168]Jaeschke H,Smith CW.Mechanisms of neutrophil-induced parenchymal cell injury[J].J Leukoc Biol,1997,61(6):647-653.
[169]Li RK,Mickle DA,Weisel RD,et al.Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury[J].Ann Thorac Surg,2001,72(6):1957-1963.
[170]Tomita S,Mickle DA,Weisel RD,et al.Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation[J].J Thorac Cardiovasc Surg,2002,123(6):1132-1140.
[171]Vulliet PR,Greeley M,Hal loran SM,et al.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J].Lancet,2004,363(9411):783-784.
[172]Kocher AA,Schuster MD,Szabolcs M J,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7(4):430-436.
[173]伟哉,郭国庆.用BrdU标记技术观察大鼠脊髓上胸段灰质细胞的分化发育[J].解 剖学报,2000,31(4):289-291.
[174]Nemoto R,Hattori K,Sasaki A,et al.Estimations of the S phase fraction in situ in transitional cell carcinoma of the renal pelvis and ureter with bromodeoxyuridine labeling [J].Br J Urol,1989,64(4):339-344.
[175]周秀华,田沈.美托洛尔和雷米普利对急性心肌梗死左室重构和血浆脑钠素影响的比较[J].中国现代医学杂志,2006,16(7):1003-1005.
[176]汪进益,范慧敏,刘中民.犬心肌缺血再灌注损伤心电图Ⅱ导联QRS波群演变的观察[J].中国实验动物学报,2007,15(2):15-18.
[177]Berger R,Huelsman M,Strecker K,et al.B-type natriuretic peptide predicts sudden death in patients with chronic heart failure[J].Circulation,2002,105(20):2392-2397.
[178]张劲林,王方正,张澍,等.脑利钠肽对新生大鼠心室肌细胞缝隙连接蛋白Cx43含量的影响[J].中国心脏起搏与心电生理杂志,2005.19(4):295-297.
[179]Yama GH,Yoshida J,Yamamota K,et al.Elavation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricularhypert rophy[J].J Am Coll Cardiol,2004,43:55-60.
[180]Gackowski A,Lsnard R,Golmard JL,et al.Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure[J].Eur Heart J,2004,25(20):1788-1796.
[181]Maisel AS,Krishnaswamy P,Nowak RM,et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J].N Engl J Med,2002,347:161-167.
[182]Martin-Du Pan RC,Ricou F.Use of brain natriuetic peptide(BNP)in the diagnosis and treatment of heart failure[J].Rev Med Suisse Romande,2003,123(2):125-128.
[183]张悟棠,王凤芝,巩书文,等.脑钠素在评价冠心病介入治疗改善心功能中的价值[J].中国药物与临床,2005,11(5):831-833.
[184]孙彦洵,周江,杨晓.小鼠胚胎干细胞体外定向心肌细胞分化的研究[J].中华心血管病杂志,2001,29(10):601-604.
[1]Anversa P,Nadal-Ginard B.Myocyte renewal and ventricular remodeling[J].Nature,2002,415(6868):240-243.
[2]卢新政,黄峻.心肌成形术的进展[J].中国循环杂志,2002,17(5):399-400.
[3]钱海燕,杨跃进.干细胞心肌再生的移植路径研究进展[J].心血管病学进展,2006,27(4):449-453.
[4]Soonpaa MH,Koh GY,Klug MG,et al.Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium[J].Science,1994,264(5155):98-101.
[5]朱洪生,钟竑,卫洪超,等.自体骨骼肌卫星细胞移植治疗急性心肌梗死的实验研究[J].中华医学杂志,2000,80(11):873-875.
[6]崔勇,陆方林,梅举,等.左心室成形术结合骨骼肌成肌细胞移植治疗心肌梗死后心力衰竭[J].第二军医大学学报,2005,26(9):975-978.
[7]Athanasuleas CL,Stanley AW Jr,Buckberg GD,et al.Surgical anterior ventricular endocardial restoration(SAVER)in the dilated remodeled ventricle after anterior myocardial infarction.RESTORE group.Reconstructive Endoventricular Surgery,returning Torsion Original Radius Elliptical Shape to the LV[J].J Am Coll Cardiol,2001,37(5):1199-1209.
[8]黄佐,葛均波.细胞移植治疗心血管疾病研究现状[J].第二军医大学学报,2004,25(9):929-932.
[9]Min JY,Yang Y,Converso KL,et al.Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats[J].J Appl Physiol,2002,92(1):288-296.
[10]Kizana E,Ginn SL,Allen DG,et al.Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling[J].Circulation,2005,111(4):394-398.
[11]Orlic D,Kajstura J,Chimenti S,et al.Bone marrow cells regenerate infarcted myocardium [J].Nature,2001,410(6829):701-705.
[12]Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans[J].Circulation,2002,106(15):1913-1918.
[13]Jain M,DerSimonian H,Brenner DA,et al.Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction[J].Circulation,2001,103(14):1920-1927.
[14]Roell W,Lu Z J,Bloch W,et al.Cellular cardiomyoplasty improves survival after myocardial injury[J].Circulation,2002,105(20):2435-2441.
[15]Li RK,Jia ZQ,Weisel RD,et al.Smooth muscle cell transplantation into myocardial scar tissue improves heart function[J].J Mol Cell Cardiol,1999,31(3):513-522.
[16]Feld Y,Melamed-Frank M,Kehat I,et al.Electrophysiological modulation of cardiomyocytic tissue by transfected fibroblasts expressing potassium channels:a novel strategy to manipulate excitability[J].Circulation,2002,105(4):522-529.
[17]Zuk PA,Zhu M,Mizuno H,et al.Multilineage cells from human adipose tissue:implications for cell-based therapies[J].Tissue Eng,2001,7(2):211-228.
[18]Fuchs E,Tumbar T,Guasch G.Socializing with the neighbors:stem cells and their niche[J].Cell,2004,116(6):769-778.
[19]Potapova I,Plotnikov A,Lu Z,et al.Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers[J].Circ Res,2004,94(7):952-959.
[20]Kamihata H,Matsubara H,Nishiue T,et al.Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts,angiogenic ligands,and cytokines[J].Circulation,2001,104(9):1046-1052.
[21]连锋,朱洪生,郑家豪,等.骨髓间质干细胞体外转化为肌细胞的研究[J].中华实验外科杂志,2002,19(5):454-456.
[22]Orlic D,Kajstura J,Chimenti S,et al.Mobilized bone marrow cells repair the infarcted heart,improving function and survival[J].Proc Natl Acad Sci USA,2001,98(18):10344-10349.
[23]Kocher AA,Schuster MD,Szabolcs MJ,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7(4):430-436.
[24]Vogel G.Harnessing the power of stem cells[J].Science,1999,283(5407):1432-1434.
[25]Murry CE,Soonpaa MH,Reinecke H,et al.Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts[J].Nature,2004,428(6983):664-668.
[26]Balsam LB,Wagers A J,Christensen JL,et al.Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium[J].Nature,2004,428(6983):668-673.
[27]Kajstura J,Rota M,Whang B,et al.Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion[J].Circ Res,2005,96(1):127-137.
[28]Assmus B,Schachinger V,Teupe C,et al.Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction(TOPCARE-AMI)[J].Circulation,2002,106(24):3009-3017.
[29]Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[30]Menasche P,Hagege AA,Scorsin M,et al.Myoblast transplantation for heart failure[J].Lancet,2001,357(9252):279-280.
[31]Menasche P,Hagege AA,Vilquin JT,et al.Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction[J].J Am Coll Cardiol,2003,41(7):1078-1083.
[32]Leobon B,Garcin I,Menasche P,et al.Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host[J].Proc Natl Acad Sci USA,2003,100(13):7808-7811.
[33]Hamano K,Nishida M,Hirata K,et al.Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease:clinical trial and preliminary results[J].Jpn Circ J,2001,65(9):845-847.
[34]Schachinger V,Assmus B,Britten MB,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction:final one-year results of the TOPCARE-AMI Trial[J].J Am Coll Cardiol,2004,44(8):1690-1699.
[35]Britten MB,Abolmaali ND,Assmus B,et al.Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction(TOPCARE-AMI):mechanistic insights from serial contrast-enhanced magnetic resonance imaging[J].Circulation,2003,108(18):2212-2218.
[36]Perin EC,Dohmann HF,Borojevic R,et al.Transendocardial,autologous bone marrow cell transplantation for severe,chronic ischemic heart failure[J].Circulation,2003,107(18):2294-2302.
[37]Kuethe F,Richartz BM,Kasper C,et al.Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans[J].Int J Cardiol,2005,100(3):485-491.
[38]Janssens S,Dubois C,Bogaert J,et al.Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction:double-blind,randomised controlled trial[J].Lancet,2006,367(9505):113-121.
[39]蒋文慧,马爱群.骨髓干细胞动员治疗缺血性心脏病研究进展[J].中国循环杂志,2003,83(21):1923-1925.
[40]Suarez de Lezo J,Torres A,Herrera I,et al.Effects of stem-cell mobilization with recombinant human granulocyte colony stimulating factor in patients with percutaneously revascularized acute anterior myocardial infarction[J].Rev Esp Cardiol,2005,58(3):253-261.
[41]Wang Y,Tagil K,Ripa RS,et al.Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms,left ventricular perfusion and function in patients with severe chronic ischemic heart disease[J].Int J Cardiol,2005,100(3):477-483.
[42]李延林,葛均波,钱菊英,等.急诊经冠状动脉自体骨髓单个核细胞移植治疗急性心肌梗死的临床研究(TCTSTAMI)[J].中国介入心脏病学杂志,2005,13(3):142-145.
[43]葛均波,李延林,钱菊英,等.陈旧性前壁心肌梗死患者自体骨髓单个核细胞移植后左室心肌灌注及收缩功能的变化[J].中国介入心脏病学杂志,2004,12(5):261-264.
[44]黄榕羽中,姚康,葛均波,等.经冠状动脉骨髓单个核细胞移植治疗原发性扩张型心肌病的安全性与疗效近期观察[J].中华心血管病杂志,2006,34(2):111-113.
[45]李占全,张明,金元哲,等.粒细胞集落刺激因子动员自体骨髓外周血干细胞移植治疗急性心肌梗死的临床研究[J].中华心血管病杂志,2006,34(2):99-102.
[46]王建安,谢小洁,何红,等.骨髓间质干细胞移植治疗原发性扩张型心肌病的疗效与安全性[J].中华心血管病杂志,2006,34(2):107-110.
[47]窦克非,杨跃进,杨伟宪,等.成体犬骨骼肌成肌细胞移植于急性心肌梗死区的试验研究[J].中华心血管病杂志,2005,33(11):1033-1036.
[48]Rafii S,Lyden D.Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J].Nat Med,2003,9(6):702-712.
[49]Pagani FD,DerSimonian H,Zawadzka A,et al.Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans.Histological analysis of cell survival and differentiation[J].J Am Coll Cardiol,2003,41(5):879-888.
[50]Barbash IM,Chouraqui P,Baron J,et al.Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium:feasibility,cell migration,and body distribution [J]. Circulation, 2003,108(7): 863-868.
[51] Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine [J]. Genes Dev, 2005,19(10): 1129-1155.
[52] Akashi K, Traver D, Zon LI. The complex cartography of stem cell commitment [J]. Cell, 2005,121(2): 160-162.
[53] Conrad C, Huss R. Adult stem cell lines in regenerative medicine and reconstructive surgery [J]. J Surg Res, 2005,124(2): 201-208.
[54] Reinecke H, Zhang M, Bartosek T, et al. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts [J]. Circulation, 1999,100(2): 193-202.
[55] Ge J, Li Y, Qian J, et al. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI) [J]. Heart, 2006,92(12): 1764-1767.
[56] Ciulla MM, Ferrero S, Lazzari L, et al. The translocation of marrow MNCs after experimental myocardial cryoinjury is proportional to the infarcted area [J]. Transfusion, 2004,44(2): 239-244.
[57] Siminiak T, Fiszer D, Jerzykowska O, et al. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial [J]. Eur Heart J, 2005,26(12): 1188-1195.
[58] Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts [J]. Nat Med, 2003,9(9): 1195-1201.
[59] Vicario J, Campos C, Piva J, et al. Transcoronary sinus administration of autologous bone marrow in patients with chronic refractory stable angina Phase 1 [J]. Cardiovasc Radiat Med, 2004, 5(2): 71-76.
[60] Aicher A, Brenner W, Zuhayra M, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling [J]. Circulation, 2003, 107(16): 2134-2139.
[61]王建安.干细胞移植治疗心肌梗死的前景[J].中华急诊医学杂志,2006,15(4):304-305.
[62]Yau TM,Tomita S,Weisel RD,et al.Beneficial effect of autologous cell transplantation on infarcted heart function:comparison between bone marrow stromal cells and heart cells[J].Ann Thorac Surg,2003,75(1):169-176.
[63]Ittrich H,Lange C,Dahnke H,et al.Labeling of mesenchymal stem cells with different superparamagnetic particles of iron oxide and detectability with MRI at 3T[J].Rofo,2005,177(8):1151-1163.
[64]Kang H J,Kim HS,Zhang SY,et al.Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction:the MAGIC cell randomised clinical trial[J].Lancet,2004,363(9411):751-756.
[65]Vulliet PR,Greeley M,Halloran SM,et al.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J].Lancet,2004,363(9411):783-784.
[66]Yoon YS,Park JS,Tkebuchava T,et al.Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction[J].Circulation,2004,109(25):3154-3157.
[67]Rubio D,Garcia-Castro J,Martin MC,et al.Spontaneous human adult stem cell transformation[J].Cancer Res,2005,65(8):3035-3039.
[68]Zhang YM,Hartzell C,Narlow M,et al.Stem cell-derived cardiomyocytes demonstrate arrhythmic potential[J].Circulation,2002,106(10):1294-1299.
[69]Marx J.Cancer research.Mutant stem cells may seed cancer[J].Science,2003,301(5638):1308-1310.
[70]Ii M,Losordo DW.Transplant graft vasculopathy:a dark side of bone marrow stem cells[J]?Circulation,2003,108(25):3056-3058.