缺血后适应基础上骨髓间充质干细胞移植对大鼠移植肺缺血再灌注损伤的保护作用
|
摘要
第一部分
改良三袖套法建立大鼠左肺原位移植动物模型
目的采用改良袖套法技术建立大鼠同种异体左肺移植模型。方法对供肺获取、套管制作、自体肺切除、血管和气管袖套套接技术进行改进。30例清洁级SD大鼠左供肺获取后置于40C的LPDG液保存3小时,随后行肉眼直视下同种异体左肺移植术,再灌注4h后阻断右肺门,分别测定阻断前后气道压力、动脉血气变化、肺湿/干重比率及光镜下肺组织结构变化。评价该模型复制移植物缺血再灌注损伤的能力。结果同种异体左肺移植模型在肉眼直视下单人完成,供受体动静脉和支气管套管吻合时间分别为:肺动脉(5±1)min、肺静脉(9±4)min、支气管(2±0.5)min。总手术时间(59±10)min。手术成功率90%(27/30),术后生存率100%。实验结果显示该模型成功复制出同种异体肺移植缺血再灌注损伤的变化。结论本模型符合大鼠肺移植模型建立的优点,全部操作在肉眼直视下单人完成;供肺的获取较为快速,使用的套管更简单,套管技术趋于简化,肺移植时血管套接技术成功率高,整体手术时间操作缩短。该模型复制出移植肺缺血再灌注损伤的变化,是适合肺移植缺血再灌注损伤研究的理想模型。
第二部分
骨髓间充质干细胞的分离、培养、鉴定、标记及其对大鼠移植肺缺血再灌注损伤的保护作用
目的分离、培养、鉴定和标记骨髓间充质干细胞(BMSCs),观察BMSCs对大鼠左肺移植物缺血再灌注损伤的保护作用并探讨其作用机制。方法以SD大鼠为供受体,采用改良袖套法技术建立同种异体左肺移植模型。设立假手术组(A组)、I/R组(B组)和BMSCs组(C组),每组n=7,离体供肺静脉40C的LPDG液逆行灌注,灌注后行左肺原位移植,移植肺再灌注4h后,阻断右肺门,测量气道压力,动脉血PaO2、PaCO2。随后处死大鼠,分别测定:肺W/D比率、肺组织中SOD活性、MDA含量、MPO活性;光镜观察移植物病理组织学变化;RT-PCR和Western-blot了解旁分泌因子VEGF的表达;ELISA检测受鼠血浆中TNF-a和IL-10的变化;免疫组化检测TNF-a和bcl-2表达情况;TUNEL法检测移植肺细胞凋亡水平。结果与假手术组相比,I/R组气道压力升高、PaO2下降、肺W/D比率上升,SOD活性降低,MDA含量和MPO活性升高(P<0.01),表明I/R组相对于假手术组确实造成了明显的缺血再灌注损伤;与I/R组相比,BMSCs组气道压力降低、PaO2上升、肺W/D比率下降,SOD活性增高,MDA含量和MPO活性下降(P<0.01);与I/R组相比,BMSCs组:血浆TNF-a水平降低,IL-10水平升高;病理检查肺泡间质水肿明显减轻,炎症细胞浸润减少,肺泡腔内水肿液和红细胞少见;免疫组化TNF-a表达减弱、bcl-2表达增强(P<0.01);TUNEL法检测移植肺细胞凋亡减少(P<0.01)。基因和蛋白水平检测显示BMSCs组肺组织旁分泌因子VEGF较假手术组、I/R组明显升高(P<0.01)。结论(1)氧化损伤等指标检测表明I/R组确实复制了移植肺的IRI;BMSCs移植能减轻移植肺的缺血-再灌注损伤。(2)BMSCs通过其抗氧化、抗炎、抗凋亡和旁分泌效应等抗损伤、促组织修复等多种途径明显减轻移植肺缺血再灌注损伤,提高肺移植术后早期肺功能。因此BMSCs移植可成为预防和减轻肺移植术后缺血再灌注损伤的一种有益尝试。
第三部分缺血后适应基础上骨髓间充质干细胞移植对大鼠移植肺缺血再灌注损伤的保护作用
目的观察缺血后适应(I-postC)基础上BMSCs移植对大鼠同种异体左肺移植物缺血再灌注损伤的保护作用并探讨其作用机制。方法以SD大鼠为供受体,采用改良三袖套法技术建立同种异体左肺移植模型。设立I/R组(A组), I-postC组(B组),BMSCs组(C组)和I-postC + BMSCs组(D组),每组n=14,离体供肺静脉40C的LPDG液逆行灌注,灌注后行左肺原位移植,移植肺再灌注4h和72h后,分别随机抽取大鼠7只阻断右肺门,测量气道压力,动脉血PaO2、PaCO2。随后处死大鼠测定:肺W/D比率、肺组织中SOD活性、MDA含量、MPO活性;光镜观察移植物病理组织学变化;RT-PCR和Western-blot了解旁分泌因子VEGF的表达;ELISA检测受鼠血浆中TNF-a、IL-10、G-CSF和GM-CSF的变化;免疫组化检测TNF-a和bcl-2表达情况;TUNEL法检测移植肺细胞凋亡水平。免疫荧光法检测肺组织中BMSCs的定位情况。结果基因和蛋白水平检测显示单纯BMSCs组、I-postC+BMSCs组肺组织旁分泌因子VEGF表达较I/R组、I-postC组明显升高(P<0.01); G-CSF,GM-CSF(72h)明显升高(P<0.01)。与I/R组比较,I-postC组、BMSCs组、I-postC+BMSCs组:TNF-a明显降低,IL-10明显升高(P<0.01);气道压力降低、PaO2上升、肺W/D下降、SOD活性增高、MDA含量和MPO活性下降(P<0.01);bcl-2表达增强,TUNEL法检测移植肺细胞凋亡减少(P<0.01)。与I/R组、I-postC组、BMSCs组相比,光镜检查I-postC+BMSCs组肺泡间质水肿减轻最显著,炎性细胞浸润、肺泡腔内水肿和渗出改变减轻最明显。免疫荧光法检测72h取的肺组织,BMSCs在肺组织中定位,主要分布在肺细支气管壁周围。结论在I-postC的基础上,再行BMSCs移植,减轻移植肺缺血再灌注损伤的程度最显著。I-postC基础上BMSCs移植减轻移植肺IRI、提高肺移植术后早期肺功能的机制与其抗氧化、抗炎、抗凋亡、旁分泌效应和干细胞归巢等密切相关,并可能与I-postC先减轻移植肺IRI,改善BMSCs存活的微环境,提高BMSCs迁移进入肺组织的“质”和“量”有关。因此I-postC基础上BMSCs移植可成为预防和减轻同种异体肺移植物IRI的一种全新的策略。
Part1.
The Improvements in Establishment of Rat Orthotopic Left Lung Transplantation Model.
Objective To establish rat orthotopic left lung allograft transplantation model by improved techniques. Methods This study improved the traditional cuff technique in many aspects, including graft retrieval, cuff self-making, recipient pneumonoresection,“muff-like”vessel and trachea anastomosis techniques. In a group with 30 pairs of clean-grade SD rats, the left lung allograft was stored at 4 oC LPDG solution for 3 h, and then the left lung was transplanted into the recipient rat without microscope. When the transplanted lung had been reperfused for 4 h. Airway pressure, blood gas analysis were detected before and after the right hilus of lung was block up, then left lung was removed, and W/D, histological changes under microscopy were determined. The reproducible ability of this model about ischemic- reperfusion injury of donor lung was evaluated. Results 30 pairs of rats receiving transplantation were performed the anastomosis of pulmonary artery, pulmonary vein and bronchus by single person without microscope. The time consuming was (5±1)min, (9±4)min(,2±0.5)minutes respectively. The total operational time consuming was (59±10)min. The operation successful rate was 90%, survival rate arrived 100%. The experimental outcome demonstrated that the model could duplicated the change of the ischemia-reperfusion injury. Conclusion The merit of this model corresponds with the construction of rat lung transplantation model. All the manipulations were performed by single person without microscope. The harvesting of donor lung was so fast that ischemic time was nearly 0 min. The cuff structure and the anastomosis technique were simpler than before. The improved“muff-like”technique increased the successful rate and shortened the total operational time consuming. This model duplicated the changes of ischemia reperfusion injury on lung allograft, and was demonstrated to be an ideal and suitable model for some researches just like IRI of donor lung .
Part2.
BMSCs Were Isolated, Cultivated, Identified and Marked,and Its Protective Effects on Ischemia-reperfusion Injury of Pulmonary Allograft in Rats
Objective Bone marrow stromal stem cells were isolated, cultivated, identified and marked,and its protective effects on ischemia-reperfusion injury of pulmonary allograft in rats and explore the mechanisms. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient by improved muff-like technique. Three groups of rats were examined. The donors in group 1 were sham operated,the donors in group 2 sufferd from ischemia-reperfusion injury,the donors in group 3 were received BMSCs .Each group have seven recipient. The donor lungs were all ex vivo reperfused by 4oC LPDG through pulmonary vein . After the left lung allograft was reperfused for 4 hours, we blocked the hilum of right lung, then measured airway pressure and made arterial blood gas analysis to measure PaO2 and PaCO2 .At last, rat was executed. Lung allograft tissue was harvested to be detected. W/D ratio, superoxide dismutase(SOD) activity, malondialdehyde (MDA) contents and myeloperoxidase(MPO) activity were detected. Graft pathologic histology was examined under light microscope. The message of expression of VEGF in donor lung tissue was measured by Real-time PCR and Western-blot. The content of TNF- a and IL-10 were quantified by ELISA. The expression of TNF-a、and bcl-2 were detected by immunohistochemical staining. Apoptotic cell death was determined by TUNEL. Results Compared with the sham operation group , the airway pressure, PaO2 ,the activity of SOD decreased and W/D ratios, content of MDA, activity of MPO increased(P<0.01)in the ischemia-reperfusion group,which demonstrated ischemia-reperfusion injury do occurred in the ischemia-reperfusion group. Compared with the ischemia-reperfusion group, the airway pressure, PaO2 ,the activity of SOD increased and W/D ratios, content of MDA, activity of MPO decreased(P<0.01)in the ischemia-reperfusion group. In the group of BMSCs, tissue edema, interstitial inflammation and exudation alleviated under light microscope, lower expression of TNF- a and higher expression of IL-10 were detected by ELISA(P<0.01), lower expression of TNF- a and higher expression of bcl-2 were detected by immunohistochemistry(P<0.01),Less apoptotic cells were found by TUNEL(P<0.01). Paracrine secretion cytokine of VEGF in the group of BMSCs was obviously higher than the sham operation group and the ischemia-reperfusion group (P<0.01) . Conclusion (1)Compared with the sham operation group , ischemia-reperfusion injury do occurred in the ischemia-reperfusion group.The transplantations of BMSCs reduced ischemic-reperfusion injury of lung allograft. (2) BMSCs reduced ischemic-reperfusion injury of lung allograft through means of anti-oxidative, anti-inflammatory and anti- apoptosis, paracrine secretion effect.So the transplantations of BMSCs may become a beneficial try which can prevent and reduce the IRI of lung allografts.
Part3.
Protective Effects Brought by Transplantations of Bone Marrow Stromal Stem Cells Based on Ischemic Postconditioning upon Ischemia- reperfusion Injury of Pulmonary Allograft in Rats
Objective To investigate protective effects brought by transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats and explore the mechanisms. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient with improved muff-like techniques. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient with improved muff-like techniques. The experiment was divided into four groups: In group A,open pulmonary blood flow directly to replicate ischemia-reperfusion injury . In group B, the donor lung suffered ischemic postconditioning before IRI. In group C, administration of BMSCs after IRI. In group D, administration of BMSCs after ischemic postconditioning. Each group have fourteen recipient. Then the left lung orthotopic transplantation was performed. After the left lung allograft was reperfused for 4 hours and 72 hours, extract seven rats randomly .,we blocked the hilum of right lung, then measured airway pressure and made arterial blood gas analysis to measure PaO2 and PaCO2 . At last, rat was executed. Lung allograft tissue was harvested to be detected W/D ratio, superoxide dismutase (SOD) activity, malondialdehyde (MDA) contents and myeloperoxidase(MPO) activity. Graft pathologic histology was examined under light microscope. The message of expression of VEGF in donor lung tissue was measured by Real-time PCR and Western-blot. The content of TNF- a , IL-10, G-CSF and GM-CSF were quantified by ELISA. The expression of TNF-a、and bcl-2 were detected by immunohistochemical staining. Apoptotic cell death was determined by TUNEL. Localization of BMSCs was detected through immumofluorescence method. Results Compared with group A and B, paracrine secretion cytokine of VEGF which detected by Real-time PCR and Western-blot was obviously increased in group C and D,so the G-CSF,GM-CSF detected by ELISA. Compared with group A , the airway pressure, PaO2 ,the activity of SOD decreased and W/D ratios, content of MDA, activity of MPO increased(P<0.01)in group B,C and D.TNF- a decreased ,IL-10 increased(P<0.01). Lower expression of TNF- a and higher expression of bcl-2 were detected by immunohistochemistry(P<0.01),Less apoptotic cells were found by TUNEL(P<0.01). In group D, tissue edema, interstitial inflammation and exudation alleviated significantly under light microscope. Through immunofluorescence method,we detected BMSCs were located in lung tissue after 72 hours. Conclusion Protective effects brought by transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats were significant.Its mechanisms may through means of anti-oxidative, anti-inflammatory and anti- apoptosis, paracrine secretion effect and homing of BMSCs.Reduce ischemic-reperfusion injury of lung allograft by ischemic postconditioning firstly,and then administration of BMSCs may improve the microenvironment of which BMSCs survived. This study demonstrated that the transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats may become a new strategy, which can reduce the IRI of lung allografts.
改良三袖套法建立大鼠左肺原位移植动物模型
目的采用改良袖套法技术建立大鼠同种异体左肺移植模型。方法对供肺获取、套管制作、自体肺切除、血管和气管袖套套接技术进行改进。30例清洁级SD大鼠左供肺获取后置于40C的LPDG液保存3小时,随后行肉眼直视下同种异体左肺移植术,再灌注4h后阻断右肺门,分别测定阻断前后气道压力、动脉血气变化、肺湿/干重比率及光镜下肺组织结构变化。评价该模型复制移植物缺血再灌注损伤的能力。结果同种异体左肺移植模型在肉眼直视下单人完成,供受体动静脉和支气管套管吻合时间分别为:肺动脉(5±1)min、肺静脉(9±4)min、支气管(2±0.5)min。总手术时间(59±10)min。手术成功率90%(27/30),术后生存率100%。实验结果显示该模型成功复制出同种异体肺移植缺血再灌注损伤的变化。结论本模型符合大鼠肺移植模型建立的优点,全部操作在肉眼直视下单人完成;供肺的获取较为快速,使用的套管更简单,套管技术趋于简化,肺移植时血管套接技术成功率高,整体手术时间操作缩短。该模型复制出移植肺缺血再灌注损伤的变化,是适合肺移植缺血再灌注损伤研究的理想模型。
第二部分
骨髓间充质干细胞的分离、培养、鉴定、标记及其对大鼠移植肺缺血再灌注损伤的保护作用
目的分离、培养、鉴定和标记骨髓间充质干细胞(BMSCs),观察BMSCs对大鼠左肺移植物缺血再灌注损伤的保护作用并探讨其作用机制。方法以SD大鼠为供受体,采用改良袖套法技术建立同种异体左肺移植模型。设立假手术组(A组)、I/R组(B组)和BMSCs组(C组),每组n=7,离体供肺静脉40C的LPDG液逆行灌注,灌注后行左肺原位移植,移植肺再灌注4h后,阻断右肺门,测量气道压力,动脉血PaO2、PaCO2。随后处死大鼠,分别测定:肺W/D比率、肺组织中SOD活性、MDA含量、MPO活性;光镜观察移植物病理组织学变化;RT-PCR和Western-blot了解旁分泌因子VEGF的表达;ELISA检测受鼠血浆中TNF-a和IL-10的变化;免疫组化检测TNF-a和bcl-2表达情况;TUNEL法检测移植肺细胞凋亡水平。结果与假手术组相比,I/R组气道压力升高、PaO2下降、肺W/D比率上升,SOD活性降低,MDA含量和MPO活性升高(P<0.01),表明I/R组相对于假手术组确实造成了明显的缺血再灌注损伤;与I/R组相比,BMSCs组气道压力降低、PaO2上升、肺W/D比率下降,SOD活性增高,MDA含量和MPO活性下降(P<0.01);与I/R组相比,BMSCs组:血浆TNF-a水平降低,IL-10水平升高;病理检查肺泡间质水肿明显减轻,炎症细胞浸润减少,肺泡腔内水肿液和红细胞少见;免疫组化TNF-a表达减弱、bcl-2表达增强(P<0.01);TUNEL法检测移植肺细胞凋亡减少(P<0.01)。基因和蛋白水平检测显示BMSCs组肺组织旁分泌因子VEGF较假手术组、I/R组明显升高(P<0.01)。结论(1)氧化损伤等指标检测表明I/R组确实复制了移植肺的IRI;BMSCs移植能减轻移植肺的缺血-再灌注损伤。(2)BMSCs通过其抗氧化、抗炎、抗凋亡和旁分泌效应等抗损伤、促组织修复等多种途径明显减轻移植肺缺血再灌注损伤,提高肺移植术后早期肺功能。因此BMSCs移植可成为预防和减轻肺移植术后缺血再灌注损伤的一种有益尝试。
第三部分缺血后适应基础上骨髓间充质干细胞移植对大鼠移植肺缺血再灌注损伤的保护作用
目的观察缺血后适应(I-postC)基础上BMSCs移植对大鼠同种异体左肺移植物缺血再灌注损伤的保护作用并探讨其作用机制。方法以SD大鼠为供受体,采用改良三袖套法技术建立同种异体左肺移植模型。设立I/R组(A组), I-postC组(B组),BMSCs组(C组)和I-postC + BMSCs组(D组),每组n=14,离体供肺静脉40C的LPDG液逆行灌注,灌注后行左肺原位移植,移植肺再灌注4h和72h后,分别随机抽取大鼠7只阻断右肺门,测量气道压力,动脉血PaO2、PaCO2。随后处死大鼠测定:肺W/D比率、肺组织中SOD活性、MDA含量、MPO活性;光镜观察移植物病理组织学变化;RT-PCR和Western-blot了解旁分泌因子VEGF的表达;ELISA检测受鼠血浆中TNF-a、IL-10、G-CSF和GM-CSF的变化;免疫组化检测TNF-a和bcl-2表达情况;TUNEL法检测移植肺细胞凋亡水平。免疫荧光法检测肺组织中BMSCs的定位情况。结果基因和蛋白水平检测显示单纯BMSCs组、I-postC+BMSCs组肺组织旁分泌因子VEGF表达较I/R组、I-postC组明显升高(P<0.01); G-CSF,GM-CSF(72h)明显升高(P<0.01)。与I/R组比较,I-postC组、BMSCs组、I-postC+BMSCs组:TNF-a明显降低,IL-10明显升高(P<0.01);气道压力降低、PaO2上升、肺W/D下降、SOD活性增高、MDA含量和MPO活性下降(P<0.01);bcl-2表达增强,TUNEL法检测移植肺细胞凋亡减少(P<0.01)。与I/R组、I-postC组、BMSCs组相比,光镜检查I-postC+BMSCs组肺泡间质水肿减轻最显著,炎性细胞浸润、肺泡腔内水肿和渗出改变减轻最明显。免疫荧光法检测72h取的肺组织,BMSCs在肺组织中定位,主要分布在肺细支气管壁周围。结论在I-postC的基础上,再行BMSCs移植,减轻移植肺缺血再灌注损伤的程度最显著。I-postC基础上BMSCs移植减轻移植肺IRI、提高肺移植术后早期肺功能的机制与其抗氧化、抗炎、抗凋亡、旁分泌效应和干细胞归巢等密切相关,并可能与I-postC先减轻移植肺IRI,改善BMSCs存活的微环境,提高BMSCs迁移进入肺组织的“质”和“量”有关。因此I-postC基础上BMSCs移植可成为预防和减轻同种异体肺移植物IRI的一种全新的策略。
Part1.
The Improvements in Establishment of Rat Orthotopic Left Lung Transplantation Model.
Objective To establish rat orthotopic left lung allograft transplantation model by improved techniques. Methods This study improved the traditional cuff technique in many aspects, including graft retrieval, cuff self-making, recipient pneumonoresection,“muff-like”vessel and trachea anastomosis techniques. In a group with 30 pairs of clean-grade SD rats, the left lung allograft was stored at 4 oC LPDG solution for 3 h, and then the left lung was transplanted into the recipient rat without microscope. When the transplanted lung had been reperfused for 4 h. Airway pressure, blood gas analysis were detected before and after the right hilus of lung was block up, then left lung was removed, and W/D, histological changes under microscopy were determined. The reproducible ability of this model about ischemic- reperfusion injury of donor lung was evaluated. Results 30 pairs of rats receiving transplantation were performed the anastomosis of pulmonary artery, pulmonary vein and bronchus by single person without microscope. The time consuming was (5±1)min, (9±4)min(,2±0.5)minutes respectively. The total operational time consuming was (59±10)min. The operation successful rate was 90%, survival rate arrived 100%. The experimental outcome demonstrated that the model could duplicated the change of the ischemia-reperfusion injury. Conclusion The merit of this model corresponds with the construction of rat lung transplantation model. All the manipulations were performed by single person without microscope. The harvesting of donor lung was so fast that ischemic time was nearly 0 min. The cuff structure and the anastomosis technique were simpler than before. The improved“muff-like”technique increased the successful rate and shortened the total operational time consuming. This model duplicated the changes of ischemia reperfusion injury on lung allograft, and was demonstrated to be an ideal and suitable model for some researches just like IRI of donor lung .
Part2.
BMSCs Were Isolated, Cultivated, Identified and Marked,and Its Protective Effects on Ischemia-reperfusion Injury of Pulmonary Allograft in Rats
Objective Bone marrow stromal stem cells were isolated, cultivated, identified and marked,and its protective effects on ischemia-reperfusion injury of pulmonary allograft in rats and explore the mechanisms. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient by improved muff-like technique. Three groups of rats were examined. The donors in group 1 were sham operated,the donors in group 2 sufferd from ischemia-reperfusion injury,the donors in group 3 were received BMSCs .Each group have seven recipient. The donor lungs were all ex vivo reperfused by 4oC LPDG through pulmonary vein . After the left lung allograft was reperfused for 4 hours, we blocked the hilum of right lung, then measured airway pressure and made arterial blood gas analysis to measure PaO2 and PaCO2 .At last, rat was executed. Lung allograft tissue was harvested to be detected. W/D ratio, superoxide dismutase(SOD) activity, malondialdehyde (MDA) contents and myeloperoxidase(MPO) activity were detected. Graft pathologic histology was examined under light microscope. The message of expression of VEGF in donor lung tissue was measured by Real-time PCR and Western-blot. The content of TNF- a and IL-10 were quantified by ELISA. The expression of TNF-a、and bcl-2 were detected by immunohistochemical staining. Apoptotic cell death was determined by TUNEL. Results Compared with the sham operation group , the airway pressure, PaO2 ,the activity of SOD decreased and W/D ratios, content of MDA, activity of MPO increased(P<0.01)in the ischemia-reperfusion group,which demonstrated ischemia-reperfusion injury do occurred in the ischemia-reperfusion group. Compared with the ischemia-reperfusion group, the airway pressure, PaO2 ,the activity of SOD increased and W/D ratios, content of MDA, activity of MPO decreased(P<0.01)in the ischemia-reperfusion group. In the group of BMSCs, tissue edema, interstitial inflammation and exudation alleviated under light microscope, lower expression of TNF- a and higher expression of IL-10 were detected by ELISA(P<0.01), lower expression of TNF- a and higher expression of bcl-2 were detected by immunohistochemistry(P<0.01),Less apoptotic cells were found by TUNEL(P<0.01). Paracrine secretion cytokine of VEGF in the group of BMSCs was obviously higher than the sham operation group and the ischemia-reperfusion group (P<0.01) . Conclusion (1)Compared with the sham operation group , ischemia-reperfusion injury do occurred in the ischemia-reperfusion group.The transplantations of BMSCs reduced ischemic-reperfusion injury of lung allograft. (2) BMSCs reduced ischemic-reperfusion injury of lung allograft through means of anti-oxidative, anti-inflammatory and anti- apoptosis, paracrine secretion effect.So the transplantations of BMSCs may become a beneficial try which can prevent and reduce the IRI of lung allografts.
Part3.
Protective Effects Brought by Transplantations of Bone Marrow Stromal Stem Cells Based on Ischemic Postconditioning upon Ischemia- reperfusion Injury of Pulmonary Allograft in Rats
Objective To investigate protective effects brought by transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats and explore the mechanisms. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient with improved muff-like techniques. Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient with improved muff-like techniques. The experiment was divided into four groups: In group A,open pulmonary blood flow directly to replicate ischemia-reperfusion injury . In group B, the donor lung suffered ischemic postconditioning before IRI. In group C, administration of BMSCs after IRI. In group D, administration of BMSCs after ischemic postconditioning. Each group have fourteen recipient. Then the left lung orthotopic transplantation was performed. After the left lung allograft was reperfused for 4 hours and 72 hours, extract seven rats randomly .,we blocked the hilum of right lung, then measured airway pressure and made arterial blood gas analysis to measure PaO2 and PaCO2 . At last, rat was executed. Lung allograft tissue was harvested to be detected W/D ratio, superoxide dismutase (SOD) activity, malondialdehyde (MDA) contents and myeloperoxidase(MPO) activity. Graft pathologic histology was examined under light microscope. The message of expression of VEGF in donor lung tissue was measured by Real-time PCR and Western-blot. The content of TNF- a , IL-10, G-CSF and GM-CSF were quantified by ELISA. The expression of TNF-a、and bcl-2 were detected by immunohistochemical staining. Apoptotic cell death was determined by TUNEL. Localization of BMSCs was detected through immumofluorescence method. Results Compared with group A and B, paracrine secretion cytokine of VEGF which detected by Real-time PCR and Western-blot was obviously increased in group C and D,so the G-CSF,GM-CSF detected by ELISA. Compared with group A , the airway pressure, PaO2 ,the activity of SOD decreased and W/D ratios, content of MDA, activity of MPO increased(P<0.01)in group B,C and D.TNF- a decreased ,IL-10 increased(P<0.01). Lower expression of TNF- a and higher expression of bcl-2 were detected by immunohistochemistry(P<0.01),Less apoptotic cells were found by TUNEL(P<0.01). In group D, tissue edema, interstitial inflammation and exudation alleviated significantly under light microscope. Through immunofluorescence method,we detected BMSCs were located in lung tissue after 72 hours. Conclusion Protective effects brought by transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats were significant.Its mechanisms may through means of anti-oxidative, anti-inflammatory and anti- apoptosis, paracrine secretion effect and homing of BMSCs.Reduce ischemic-reperfusion injury of lung allograft by ischemic postconditioning firstly,and then administration of BMSCs may improve the microenvironment of which BMSCs survived. This study demonstrated that the transplantations of bone marrow stromal stem cells based on ischemic postconditioning upon ischemia-reperfusion injury of pulmonary allograft in rats may become a new strategy, which can reduce the IRI of lung allografts.
引文
[1]Cooper JD. Lung transplantation: a new era[J]. Ann Thorac Surg. 1987,44:447-8.
[2]Elbert p trulock, Leah B Edwards, David OTaylor, et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-first official Adult Lung and Heart-Lung Transplant Report-2004.
[3]辛育龄,蔡廉埔,胡启邦,等.人体肺移植一例报告[J].中华外科杂志,1979,17:323.
[4]陈玉平,张志泰,韩玲,等.肺移植治疗肺纤维化一例报告[J].中华外科杂志,1996,34:25.
[5]陈玉平,张志泰,区颂雷,等.1例双肺移植治疗肺动脉高压病人2年随访结果和体会[J].中华胸心血管外科杂志,2000,16:7-8.
[6]陈静瑜我国肺移植的发展和初步经验[J].中华器官移植杂志,2006,27(2):67.
[7]King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation[J]. Ann Thorac Surg. 2000,69:1681-5.
[8]Trulock, E P. Lung transplantation[J]. Am J Respir Crit Care Med. 1997,155: 789-818
[9]Fisher SM, Tribble CG, Long SM, et al. Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome[J]. Ann Thorac Surg. 2002,73:1041-7.
[10]Mccord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med. 1985,312:159-63.
[11]Al-Mehdi AB, Shuman H, Fisher AB. Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia[J]. Am J Physiol. 1997,272: 294-300.
[12]Ware LB, Golden JA, Finkbeiner WE, et al. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation[J]. Am J Respir Crit Care Med. 1999,159:980-8.
[13]Sugita M, Suzuki S, Kondo T, et al. Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution[J].Transplantation. 1999,67:349-54.
[14]Yokomise H, Ueno T, Yamazaki F, et al. The effect and optimal time of administration of verapamil on lung preservation[J]. Transplantation. 1990,49:1039-43.
[15]Pickford MA, Gower JD, Dore C, et al. Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo[J]. Transplantation. 1990,50:210-8.
[16]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J].Transplantation. 1994,58:1158-62.
[17]Krishnadasan B, Naidu BV, Byrne K, et al. The role of proinflammatory cytokines in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 2003,125:261-72
[18]Vural KM, Oz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion[J]. Eur J Cardiothorac Surg. 2000,18:348-52.
[19]Ahrens N, Tormin A, Paulus M, Roosterman D, Salama A, Krenn V, Neumann U, Scheding S. Mesenchymal stem cell content of human vertebral bone marrow[J]. Transplantation. 2004,78:925-9.
[20]Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood[J]. Br J Haematol. 2000, 109:235-42.
[21]Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN. Mesenchymal precursor cells in the blood of normal individuals[J]. Arthritis Res.2000,2:477-88.
[22]Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies[J]. Tissue Eng.2001,7:211-28.
[23]Li CD, Zhang WY, Li HL, Jiang XX, Zhang Y, Tang PH, Mao N. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation[J]. Cell Res.2005,15:539-47.
[24]G?therstr?m C, Ringdén O, Westgren M, Tammik C, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells[J]. Bone Marrow Transplant. 2003,32: 265-72.
[25]Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation[J]. Differentiation.2001, 68 :245-53.
[26]Friedenstein AJ, Gorskaja JF, Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol. 1976, 4:267-74
[27]Caplan AI. Mesenchymal stem cells[J]. J Orthop Res. 1991, 9:641-50.
[28]Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72
[29]Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003, 100: 8407～11.
[30]Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung[J]. Am J Respir Cell Mol Biol. 2005, 33:145-52.
[31]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[32]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol,2002 ,174 :11-20.
[33]许予明,宋波,秦洁,等.骨髓间充质干细胞对大鼠脑缺血再灌注损伤的保护机制[J ].国外医学?脑血管疾病分册,2004, 12 (9) : 657.
[34]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[35]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[36]Vintern - Johansen J, Edgerton TA, HoweHR, et al. Immediate functional recovery and avoidance of reperfusion injury with surgical revascularization of short - term coronaryocclusion[J]. Circukation, 1985, 72:431-39.
[37]Vinten - Johansen J, Buckberg GD, OkamotoF, et al. Superiority of surgical versus medical reperfusion after regional ischemia[J].Thorac Cardiovasc Surg, 1986, 92: 525 -34.
[38]Okamoto F, Allen BS, Buckberg GD, et al.Reperfusion conditions: importance of ensuringgentle versus sudden reperfusion during relief of coronary occlusion [J]. Thorac Cardiovas Surg, 1986, 92: 613 - 20.
[39]Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J].Physiol Heart Circ Physiol, 2003, 285: 579- 88.
[40]Shliakhto EV, GalagudzaMM, SyrenskiiAV,et al. Ischemic postconditioning of the myocardium: a new method of heart protection against reperfusion damage [J]. Ter Arkh, 2005,77: 77 - 80.
[41]Patrick S, Gilles R, Christophe P, et al.Postconditioning the human heart [J]. Circulation, 2005, 112: 2077-8.
[42]Argaud L, Gateau-Roesch J, Loufouat D, et al. Postconditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005, 111: 194-7.
[43]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[44]Staat P, Rioufol G, Piot C, et al. Postconditioning the human heart[J]. Circulation, 2005, 112: 2143-8.
[45]Yellon DM, Opie LH. Postconditioning for protection of the infarcting heart[J]. Lancet, 2006, 367: 456-8.
[1]Reis A, Giaid A, Serrick C, et al. Improved outcome of rat lung transplantation with modification of the nonsuture external cuff technique[J]. J Heart Lung Transplant. 1995,14:274-9.
[2]施新猷,顾为望.大鼠生物学特性及应用.施新猷主编.现代医学实验动物学[M].第1版,北京:人民军医出版社, 2000: 82-93.
[3]Eppinger MJ, Ward PA, Jones ML, et al. Disparate effects of nitric oxide on lung ischemia-reperfusion injury[J]. Ann Thorac Surg. 1995,60:1169-75.
[4]Eppinger MJ, Ward PA, Bolling SF, et al. Regulatory effects of interleukin-10 on lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 1996,112:1301-5.
[5]Asimacopoulos PJ, Molokhia FA, Pegg CA, et al. Lung transplantation in the rat[J]. Transplant Proc. 1971,3:583-5.
[6]MiyataM,FischerJM,FuhsM,etal. A simple method for orthotopic liver transplantation in the rat[J]. Transplantation. 1980,30:335-8.
[7]Kamada N, Calne RY. Kamada N, et al. A surgical experience with five hundred thirty liver transplants in the rat[J]. Surgery. 1983,93:64-9
[8]Mizuta T, Kawaguchi A, Nakahara K, et al. Simplified rat lung transplantation using a cuff technique[J]. Transplant Proc. 1989,21:2601-2.
[9]Mizuta T, Nakahara K, Shirakura R, et al. Total nonmicrosuture technique for rat lung transplantation[J]. J Thorac Cardiovasc Surg. 1991,102:159-60.
[10]张翀,倪一鸣,徐鹤云.大鼠同种异体左肺移植模型方法的改进[J ].中华实验外科杂志,2003,20(9):854-5.
[11]张新,陈如坤,高颖欣,等.一种新的大鼠肺移植模型[J ].中华器官移植杂志,2005,26(3):178-79.
[12]蒋志华,杨辰垣.大鼠同种异体左肺移植模型方法的建立[J ].中华实验外科杂志,1999,16(2):185-6.
[13]Kubisa B, Schmid RA, Grodzki T et al. Model of single left rat lung transplantation. Relation between surgical experience and outcomes[J]. Rocz Akad Med Bialymst. 2003,48:70-3.
[14]Santana R N, Martin B JL, Lopez G A, et al. Lung transplantation in rats: a viable experimental model[J]. Arch Bronconeumol. 2004,40:438-42.
[15]Swoboda L, Clancy DE, Donnebrink MA, et al. The influence of verapamil on lung preservation. A study on rabbit lungs with a reperfusion model allowing physiological loading[J]. Thorac Cardiovasc Surg. 1993,41:85-92.
[1]Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation: seventeenth official report-2000.
[2]King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation[J]. Ann Thorac Surg 2000,69:1681-5.
[3]Fiser SM, Tribble CG, Long SM, et al. Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome[J]. Ann Thorac Surg. 2002,73:1041-7.
[4]汪谦.主编.临床医学实验方法学[M].第一版. 2002.北京:科学出版社:307-12
[5]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods. 2001,25:402-8.
[6]Miller AL, Bowlin TL, Lukacs NW. Respiratory syncytial virus-induced chemokine production: linking viral replication to chemokine production in vitro and in vivo[J]. J Infect Dis. 2004,189:1419-30
[7]Alho HS, Salminen US, Maasilta PK, et al. Epithelial apoptosis in experimental obliterative airway disease after lung transplantation[J]. J Heart Lung Transplant. 2003,22:1014-22.
[8]Cooper JD, Vreim CE. NHLBI workshop summary. Biology of lung preservation for transplantation[J]. Am Rev Respir Dis. 1992,146:803-7.
[9]McCord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med. 1985,312:159-63.
[10]Al-Mehdi AB, Shuman H, Fisher AB. Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia[J]. Am J Physiol. 1997,272:294-300
[11]Ware LB, Golden JA, Finkbeiner WE, et al. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation[J]. Am J Respir Crit Care Med. 1999,159:980-8.
[12]Sugita M, Suzuki S, Kondo T, et al. Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution.Transplantation[J]. 1999,67:349-54.
[13]Yokomise H, Ueno T, Yamazaki F,et al. The effect and optimal time of administration of verapamil on lung preservation. Transplantation[J]. 1990,49:1039-43.
[14]Pickford MA, Gower JD, Dore C, et al. Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo[J]. Transplantation. 1990,50:210-8.
[15]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J].Transplantation. 1994,58:1158-62.
[16]Krishnadasan B, Naidu BV, Byrne K, et al. The role of proinflammatory cytokines in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 2003,125:261-72
[17]Vural KM, Oz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion[J]. Eur J Cardiothorac Surg. 2000,18:348-52.
[18]Friedenstein AJ, Gorskaja JF, Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol. 1976, 4:267-74.
[19]Caplan AI. Mesenchymal stem cells[J]. J Orthop Res. 1991 , 9:641-50.
[20]Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72
[21]Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003,100: 8407-11.
[22]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[23]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol ,2002,174 :11-20.
[24]许予明,宋波,秦洁,等.骨髓间充质干细胞对大鼠脑缺血再灌注损伤的保护机制[J ].国外医学?脑血管疾病分册,2004, 12 (9) : 657.
[25]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[26]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[27]Sch?chinger V, Erbs S, Els?sser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1210-21.
[28]Hristov M, Heussen N, Schober A, et al. Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis[J]. J Cell Mol Med, 2006, 10:727-33.
[29]Arnesen H, Lunde K, Aakhus S, et al. Cell therapy in myocardial infarction[J]. Lancet, 2007, 369: 2142-3.
[30]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: 113-21.
[31]Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (Bone marrow transfer to enhance ST-elevation infarct regeneration) trial[J]. Circulation, 2006, 113: 1287-94.
[32]Lunde K, Solheim S, Aakhus S, et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1199-209.
[33]Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium[J]. Nature, 2001, 410: 701-5.
[34]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[35]Filip S, English D, Mokry J. Issues in stem cell plasticity[J]. J Cell Mol Med, 2004, 8: 572-7.
[36]Uemura R, Xu M, Ahmad N, et al. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling[J]. Circ Res, 2006, 98: 1414-21.
[37]Gupta N, Su X, Popov B,et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice[J]. J Immunol,2007,179:1855-63.
[38]Shiraishi Y, Lee JR, Laks H, et al. Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model[J]. J Heart Lung Transplant. 1998,17:250-8.
[39]De Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation[J]. Am J Respir Crit Care Med. 2002,165:211-5.
[40]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J]. Transplantation. 1994,58:1158-62.
[41]Fehrenbach H, Schepelmann D, Albes J M, et al. pulmonary ischemia reperfusion injury :aquantitative structure and function in isolatedheart-lungs of the rat[J]. Anat Rec. 1999,255:84-9.
[42]Tutor J D, Mason C M, Dobard E, et al. Loss of compartmen talization of alveolar tumor necrosis factor after lung injury[J]. Ann J Respi CritrCare Med. 1994,149:1107-11.
[43]Palace GP, Del Vecchio PJ, Horgan MJ, et al. Release of tumor necrosis factor after pulmonary artery occlusion and reperfusion[J]. Am Rev Respir Dis. 1993,147:143-7.
[44]Donnelly RP, Dickensheets H, Finbloom DS, et al. Interleukin-10 synergize to inhibit cell- mediated immunity in vivo[J]. J Interfon Cytokin Res. 1999,19: 563-73.
[45]Krebs DL, Hilton DJ. Complication in long-term survivors of cardiac[J]. J Cell Sci. 2000;113:2813-9.
[46]Powrie F, Menon S, Coffman RL, et al. Interleukin-4 and interleukin-10 synergize to inhibits cell-mediated immunity in vivo[J]. Eur J Immunol. 1993,23:3043-9.
[47]Fischer S, Cassivi SD, Xavier AM, et al. Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation[J]. Ann Surg. 2000,231:4242-311.
[48]Garcia Velasco JA, Arici A. Apoptosis and the pathogenesis of endometriosis[J]. Semin Reprod Med. 2003,21:165-72.
[49]Di Renzo M, Rubegni P, Sbano P, et al . ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family[J]. Arch Dermatol Res. 2003,295 :175-82.
[1]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[2]Sch?chinger V, Erbs S, Els?sser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1210-21.
[3]Hristov M, Heussen N, Schober A, et al. Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis[J]. J Cell Mol Med, 2006, 10:727-33.
[4]Arnesen H, Lunde K, Aakhus S, et al. Cell therapy in myocardial infarction[J]. Lancet, 2007, 369: 2142-3.
[5]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: 113-21.
[6]Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (Bone marrow transfer to enhance ST-elevation infarct regeneration) trial[J]. Circulation, 2006, 113: 1287-94.
[7]Lunde K, Solheim S, Aakhus S, et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1199-209.
[8]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol ,2002 ,174:11-20.
[9]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[10]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[11] Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003,100: 8407-11.
[12]Zhao ZQ, Corvera JS, Halkos ME, etal. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol, 2003, 285: 579-88.
[13]Argaud L, Gateau-Roesch J, Loufouat D, etal. Postconditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005, 111: 194-7.
[14]Kin H, Zhao ZQ, Sun HY, etal. Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[15]Staat P, Rioufol G, Piot C, etal. Postconditioning the human heart[J]. Circulation, 2005, 112: 2143-8.
[16]Yellon DM, Opie LH. Postconditioning for protection of the infarcting heart[J]. Lancet, 2006, 367: 456-8.
[17]Fan Q, Yang XC, Wang SY, etal. Equivalent cardioprotective effect of " half-conditioning" and postconditioning in a canine model ofmyocardial ischemia and reperfusion[J]. Zhong hua Xin Xue Guan Bing Za Zhi, 2006, 34: 363-6.
[18]Tsang A, Hausenloy DJ, MocanuMM, etal. Postconditioning: A Form of "Modified Reperfusion" Protects the Myocardium by Activating the Phosphatidylinositol 3-Kinase-Akt Pathway[J]. Circ Res, 2004, 95: 230-2.
[19]Darling CE, J iang R, Maynard M, etal. Postconditioning via stuttering reperfusion limitsmyocardial infarct size in rabbit hearts: role of ERK1 /2[J]. Am J Physiol Heart Circ Physiol, 2005, 289: 1618-26.
[20]Zatta AJ , Kin H, Lee G, etal. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signaling[J]. Cardiovasc Res, 2006, 70: 315-24.
[21]Heusch G, BuchertA, Feldhaus S, etal. No loss of cardioprotection by postconditioning in connexin 43-deficientmice[J].Basic Res Cardiol, 2006, 101: 354-6.
[1] Krause D S, Theise N D, CollectorM I, et al. Multi2organ,multi-lineage engraftment by a single bone marrow-derived stem cell[J].Cell, 2001, 105: 369-77.
[2] Pittenger M F, Mackay A M, Beck S C, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science,1999, 284: 143-7.
[3] Ortiz L A, Gambelli F,McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003, 100: 8407-11.
[4] Gross T J, Hunninghake GW. Idiopathic pulmonary fibrosis[J]. N Engl J Med, 2001, 345: 517-25.
[5] Zander D S, Cogle C R, Theise N D, et al. Donor2Derived TypeII Pneumocytes Are Rare in the Lungs of Allogeneic Hematopoietic Cell Transplant Recipients[J]. Ann Clin Lab Sci,2006, 36: 47-52.
[6] Yuehua J, Balkrishna N, Robert E, et al. Pluripotency of mesenchymal stem cells derived from adult marrow[J]. Nature,2002, 418 : 41-9.
[7] Yamada M, Kubo H, Kobayashi S, etal. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72.
[8] Theise N D, Henegariu O, Grove J, et al. Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow[J]. Exp Hematol, 2002, 30: 1333-8.
[9] Vintern - Johansen J, Edgerton TA, HoweHR, et al. Immediate functional recovery and avoidance of reperfusion injury with surgical revascularization of short - term coronaryocclusion[J]. Circukation, 1985, 72:431-9.
[10] Vinten - Johansen J, Buckberg GD, OkamotoF, et al. Superiority of surgical versus medical reperfusion after regional ischemia[J].Thorac Cardiovasc Surg, 1986, 92: 525-34.
[11] Okamoto F, Allen BS, Buckberg GD, et al.Reperfusion conditions: importance of ensuringgentle versus sudden reperfusion during relief of coronary occlusion[J]. Thorac Cardiovas Surg, 1986, 92: 613-20.
[12] Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J].Physiol Heart Circ Physiol, 2003, 285: 579-88.
[13] Shliakhto EV, GalagudzaMM, SyrenskiiAV,et al. Ischemic postconditioning of the myocardium: a new method of heart protection against reperfusion damage[J]. Ter Arkh, 2005,77: 77 -80.
[14] Patrick S, Gilles R, Christophe P, et al.Postconditioning the human heart[J]. Circulation, 2005, 112: 2077-8.
[15]范谦,杨新春,王树岩,等.“渐处理”降低了犬心肌缺血/再灌注损伤[ J ].中华心血管病杂志, 2006, 34: 363-6.
[16] Kin H,Zhao ZQ,Sun HY,et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004,62:74-85.
[17] Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[18] Yang XM, Proctor JB, Cui L, et al. Multip le, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. Am Coll Cardiol, 2004, 44: 1103-10.
[19] Fan Q, Yang XC, Wang SY, etal. Equivalent cardioprotective effect of " half-conditioning" and postconditioning in a canine model ofmyocardial ischemia and reperfusion[J]. Zhong hua Xin Xue Guan Bing Za Zhi, 2006, 34: 363-6.
[20]Tsang A, Hausenloy DJ, MocanuMM, etal. Postconditioning: A Form of "Modified Reperfusion" Protects the Myocardium by Activating the Phosphatidylinositol 3-Kinase-Akt Pathway[J]. Circ Res, 2004, 95: 230-2.
[21]Darling CE, J iang R, Maynard M, etal. Postconditioning via stuttering reperfusion limitsmyocardial infarct size in rabbit hearts: role of ERK1 /2[J]. Am J Physiol Heart Circ Physiol, 2005, 289: 1618-26.
[22]Zatta AJ , Kin H, Lee G, etal. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signaling[J]. Cardiovasc Res, 2006, 70: 315-24.
[23]Heusch G, BuchertA, Feldhaus S, etal. No loss of cardioprotection by postconditioning in connexin 43-deficientmice[J].Basic Res Cardiol, 2006, 101: 354-6.
[24] Kirk JB, Clquhoun IW, Dark JH, et al. Lung preservation: a review of current practice and future directions[J]. Ann Thorac Surg, 1993, 56:990-1000.
[25] Shiraishi Y, Lee JR, Laks H, et al. Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model[J]. J Heart Lung Transplant, 1998, 17:250-8.
[26] Uthoff K, Zehr KJ, Lee PC, et al. Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation[J]. Ann Thorac Surg, 1995, 59:7-13.
[27] Eppinger MJ, Jones ML, Deeb GM. Pattern of injury and role of neutrophils in reperfusion injury and role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58:713-8.
[28] Gee MH, Albertine KH. Neutrophil-endothelial cell interactions in the lung[J]. Ann Rev Physiol, 1993,55:227-48.
[27] Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia reperfusion andcirculatory shock[J].. Ann Rev Pharmacol Toxicol, 1993, 33:71-90.
[29] Cretani B, Cornillet P, Dehoux M. Alveolar type II epithelial cells produce interleukin-6 in vitro and in vivo: regulation by alveolar macrophage secretoty products[J]. J Clin Invest,1994, 94:731-40.
[30] Novick RJ, Gehman KE, Ali IS, et all. Lung preservation: the importance of endothelial and alveolar type II cell integrity[J]. Ann Thorac Surg, 1996, 62:302-14.
[31] Pinsky DJ, Naka Y, chowdhury NC, et al. The nitric oxide/cyclic GMP pathway in organ transplantation:critical role in successful lung preservation[J]. Proc Natl Acad Sci, 1994, 94:731-40.
[32] Omote Y, Ikeda K, Yamazaki K, et al. The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation[J]. Surg Today, 1994, 24:616-20.
[33] Haniuda M ,Dresler CM ,Mizuta T ,et al .Free radical mediated vascular injury in lungs preserved at moderate hypo thermia [J].Ann Thorac Surg ,1995,60:1376-81.
[34] Fisher AJ,Donnelly SC, Hirani N ,et al.Elevated levels of inter- leukin- 8 in donor lungs is associated with early graft failure after lung transplantation[J]. Am J Respir Crit Care Med ,2001,163:259-65.
[35] Rabb H , Daniels F ,O'Donnell M ,et al .Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice[J]. Am J physiol ,2000,279: 525-31.
[36] Hausen B ,Bahra M ,Mueller P ,et al .Donor pretreatment with amboxol or dexamethasone fails to ameliorate reperfusion injury in experimental lung transplantation[J].Transplant,1998,11:186-94.
[37] McRacKM.Pulmonary transplantation[J].Curr Opin Anesthesiol,2000,13:53-9.
[38] Chiang CH ,WU K,Yu CP,et al.Hypothermia and PGEL produce synergistic attenuation of ischemia-reperfusion lung injury[J] .Am J Respir Crit Care Med ,1999,160:1319-23.
[39] Lockinger A ,Schutte H,Walmrath D ,et al .Protection against gas exchange abnormalities by pre-aerosolized PGE1, iloprost and nitroprusside in lung ischemia-reperfusion[J]. Transplantation,2001,71:185-93.
[40] Featherstone RL,Chamber DJ,Kelly FJ, et al.Ischemic preconditioning enhances recovery of isolated rat lungs after hypothermic preservation[J]. Ann Thorac Surg, 2000,69:237-42.
[41] Marber MS,Latchman DS,Walker JM et al.Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction[J]. Circulation,1993,88:1264-72.
[42] Nozawa Y,Miura T,Tsuchida A, et al.Chronic treatment with an ACE inhibitor,temocapril,lowers the threshold for the infarct size-limiting effect of ischemic preconditioning[J]. Cardiovasc Drugs Ther, 1999,13:151-7.
[43] Gho BC, Shoemaker RG,van den Doel MA et al. Myocardial protection by brief ischemia in noncardiac tissue[J]. Circulation, 1996,94:2193-200.
[44] Li G,chen S,Lou W, et al. The protective effects of cardiac ischemic preconditioning on lung in cardiac operation with cardiopulmonary bypass[J].Hunan Yi Ke Da Xue Xue Bao. 1998,23:41-3.
[45] Li G,Chen S,Lu E, et al. Protective effects of ischemic preconditioning on lung ischemia reperfusion injury: an in-vivo rabbit study[J]. Thorac Cardiovasc Surg, 1999,47:38-41.
[46] Luo W, Cheng S,Jiang H,et al. Effects of ischemic preconditioning on protection of canine donor lung[J].Hunan Yi Ke Da Xue Xue Bao. 1997,22:195-8.
[47] Li G, chen S,Lou W, et al. Protective effects of ischemic preconditioning on donor lung in canine lung transplantation[J]. Chest, 1998,113:1356-9.
[48] Soncul H,Oz E,Kalaycioglu S, et al. Protective effects of ischemic preconditioning on donor lung in canine lung transplantation[J]. Chest, 1999,115:1672-7.
[49] Gasparri RI,Jannis NC,Flameng WJ, et al. Ischemic preconditioning enhances donor lung preservation in the rabbit[J].Eur J Cardiothorac Surg. 1999,16:639-46.
[50] Luo W, Cheng S,Jiang H,et al. Effect of ischemic preconditioning on adenine nucleotide levels of graft lung from canine donor[J].Hunan Yi Ke Da Xue Xue Bao.1997,22:8-10.
[51] Du ZY, Hicks M, Winlaw D, Spratt P, Macdonald P. Ischemic precon- ditioning enhances donor lung preservation in the rat[J]. J Heart Lung Transplant, 1996 ,15:1258.
[52] Yellon DM, Alkliulaifi AM, Piigsley WB. Preconditioning the humanmyocardium[J]. Lancet, 1993,34:227.
[53] Li GH,Chen SX,Lou WH,Lu EX.Protective effect of ischemic preconditioning on donor lung in the canine lung transplatation[J].Chest,1998,1:1356.
[54] Cassivi SD,Liu M ,Boehler A ,et al.Transplant immunosuppression increases and prolongs transgene expression following adenoviralmediated of rat lungs [J].J Heart Lung Transplant ,2000,19:984-94.
[55] De Perrot M ,Fischer S ,Liu M ,et al. Transtracheal administracheal administration ofadenoviral-mediated human IL-10 gene to rat donpr lungs : timing of transfection and roie of early inflammation on posttransplant graft function[J] .Mol Ther ,2001,3:258.
[56] Boasquevisque CH,Mora BN,Bernstein M,Osburn WO,Nietupski J,Scheule RK,Cooper JD,Botney M,Patterson GA.Ex vovo liposome-mediated gene transfer to lung isografts[J].J Thorac Cardiovasc Surg.1998,115:38-44.
[2]Elbert p trulock, Leah B Edwards, David OTaylor, et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-first official Adult Lung and Heart-Lung Transplant Report-2004.
[3]辛育龄,蔡廉埔,胡启邦,等.人体肺移植一例报告[J].中华外科杂志,1979,17:323.
[4]陈玉平,张志泰,韩玲,等.肺移植治疗肺纤维化一例报告[J].中华外科杂志,1996,34:25.
[5]陈玉平,张志泰,区颂雷,等.1例双肺移植治疗肺动脉高压病人2年随访结果和体会[J].中华胸心血管外科杂志,2000,16:7-8.
[6]陈静瑜我国肺移植的发展和初步经验[J].中华器官移植杂志,2006,27(2):67.
[7]King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation[J]. Ann Thorac Surg. 2000,69:1681-5.
[8]Trulock, E P. Lung transplantation[J]. Am J Respir Crit Care Med. 1997,155: 789-818
[9]Fisher SM, Tribble CG, Long SM, et al. Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome[J]. Ann Thorac Surg. 2002,73:1041-7.
[10]Mccord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med. 1985,312:159-63.
[11]Al-Mehdi AB, Shuman H, Fisher AB. Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia[J]. Am J Physiol. 1997,272: 294-300.
[12]Ware LB, Golden JA, Finkbeiner WE, et al. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation[J]. Am J Respir Crit Care Med. 1999,159:980-8.
[13]Sugita M, Suzuki S, Kondo T, et al. Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution[J].Transplantation. 1999,67:349-54.
[14]Yokomise H, Ueno T, Yamazaki F, et al. The effect and optimal time of administration of verapamil on lung preservation[J]. Transplantation. 1990,49:1039-43.
[15]Pickford MA, Gower JD, Dore C, et al. Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo[J]. Transplantation. 1990,50:210-8.
[16]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J].Transplantation. 1994,58:1158-62.
[17]Krishnadasan B, Naidu BV, Byrne K, et al. The role of proinflammatory cytokines in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 2003,125:261-72
[18]Vural KM, Oz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion[J]. Eur J Cardiothorac Surg. 2000,18:348-52.
[19]Ahrens N, Tormin A, Paulus M, Roosterman D, Salama A, Krenn V, Neumann U, Scheding S. Mesenchymal stem cell content of human vertebral bone marrow[J]. Transplantation. 2004,78:925-9.
[20]Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood[J]. Br J Haematol. 2000, 109:235-42.
[21]Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN. Mesenchymal precursor cells in the blood of normal individuals[J]. Arthritis Res.2000,2:477-88.
[22]Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies[J]. Tissue Eng.2001,7:211-28.
[23]Li CD, Zhang WY, Li HL, Jiang XX, Zhang Y, Tang PH, Mao N. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation[J]. Cell Res.2005,15:539-47.
[24]G?therstr?m C, Ringdén O, Westgren M, Tammik C, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells[J]. Bone Marrow Transplant. 2003,32: 265-72.
[25]Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation[J]. Differentiation.2001, 68 :245-53.
[26]Friedenstein AJ, Gorskaja JF, Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol. 1976, 4:267-74
[27]Caplan AI. Mesenchymal stem cells[J]. J Orthop Res. 1991, 9:641-50.
[28]Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72
[29]Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003, 100: 8407～11.
[30]Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung[J]. Am J Respir Cell Mol Biol. 2005, 33:145-52.
[31]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[32]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol,2002 ,174 :11-20.
[33]许予明,宋波,秦洁,等.骨髓间充质干细胞对大鼠脑缺血再灌注损伤的保护机制[J ].国外医学?脑血管疾病分册,2004, 12 (9) : 657.
[34]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[35]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[36]Vintern - Johansen J, Edgerton TA, HoweHR, et al. Immediate functional recovery and avoidance of reperfusion injury with surgical revascularization of short - term coronaryocclusion[J]. Circukation, 1985, 72:431-39.
[37]Vinten - Johansen J, Buckberg GD, OkamotoF, et al. Superiority of surgical versus medical reperfusion after regional ischemia[J].Thorac Cardiovasc Surg, 1986, 92: 525 -34.
[38]Okamoto F, Allen BS, Buckberg GD, et al.Reperfusion conditions: importance of ensuringgentle versus sudden reperfusion during relief of coronary occlusion [J]. Thorac Cardiovas Surg, 1986, 92: 613 - 20.
[39]Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J].Physiol Heart Circ Physiol, 2003, 285: 579- 88.
[40]Shliakhto EV, GalagudzaMM, SyrenskiiAV,et al. Ischemic postconditioning of the myocardium: a new method of heart protection against reperfusion damage [J]. Ter Arkh, 2005,77: 77 - 80.
[41]Patrick S, Gilles R, Christophe P, et al.Postconditioning the human heart [J]. Circulation, 2005, 112: 2077-8.
[42]Argaud L, Gateau-Roesch J, Loufouat D, et al. Postconditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005, 111: 194-7.
[43]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[44]Staat P, Rioufol G, Piot C, et al. Postconditioning the human heart[J]. Circulation, 2005, 112: 2143-8.
[45]Yellon DM, Opie LH. Postconditioning for protection of the infarcting heart[J]. Lancet, 2006, 367: 456-8.
[1]Reis A, Giaid A, Serrick C, et al. Improved outcome of rat lung transplantation with modification of the nonsuture external cuff technique[J]. J Heart Lung Transplant. 1995,14:274-9.
[2]施新猷,顾为望.大鼠生物学特性及应用.施新猷主编.现代医学实验动物学[M].第1版,北京:人民军医出版社, 2000: 82-93.
[3]Eppinger MJ, Ward PA, Jones ML, et al. Disparate effects of nitric oxide on lung ischemia-reperfusion injury[J]. Ann Thorac Surg. 1995,60:1169-75.
[4]Eppinger MJ, Ward PA, Bolling SF, et al. Regulatory effects of interleukin-10 on lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 1996,112:1301-5.
[5]Asimacopoulos PJ, Molokhia FA, Pegg CA, et al. Lung transplantation in the rat[J]. Transplant Proc. 1971,3:583-5.
[6]MiyataM,FischerJM,FuhsM,etal. A simple method for orthotopic liver transplantation in the rat[J]. Transplantation. 1980,30:335-8.
[7]Kamada N, Calne RY. Kamada N, et al. A surgical experience with five hundred thirty liver transplants in the rat[J]. Surgery. 1983,93:64-9
[8]Mizuta T, Kawaguchi A, Nakahara K, et al. Simplified rat lung transplantation using a cuff technique[J]. Transplant Proc. 1989,21:2601-2.
[9]Mizuta T, Nakahara K, Shirakura R, et al. Total nonmicrosuture technique for rat lung transplantation[J]. J Thorac Cardiovasc Surg. 1991,102:159-60.
[10]张翀,倪一鸣,徐鹤云.大鼠同种异体左肺移植模型方法的改进[J ].中华实验外科杂志,2003,20(9):854-5.
[11]张新,陈如坤,高颖欣,等.一种新的大鼠肺移植模型[J ].中华器官移植杂志,2005,26(3):178-79.
[12]蒋志华,杨辰垣.大鼠同种异体左肺移植模型方法的建立[J ].中华实验外科杂志,1999,16(2):185-6.
[13]Kubisa B, Schmid RA, Grodzki T et al. Model of single left rat lung transplantation. Relation between surgical experience and outcomes[J]. Rocz Akad Med Bialymst. 2003,48:70-3.
[14]Santana R N, Martin B JL, Lopez G A, et al. Lung transplantation in rats: a viable experimental model[J]. Arch Bronconeumol. 2004,40:438-42.
[15]Swoboda L, Clancy DE, Donnebrink MA, et al. The influence of verapamil on lung preservation. A study on rabbit lungs with a reperfusion model allowing physiological loading[J]. Thorac Cardiovasc Surg. 1993,41:85-92.
[1]Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation: seventeenth official report-2000.
[2]King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation[J]. Ann Thorac Surg 2000,69:1681-5.
[3]Fiser SM, Tribble CG, Long SM, et al. Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome[J]. Ann Thorac Surg. 2002,73:1041-7.
[4]汪谦.主编.临床医学实验方法学[M].第一版. 2002.北京:科学出版社:307-12
[5]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods. 2001,25:402-8.
[6]Miller AL, Bowlin TL, Lukacs NW. Respiratory syncytial virus-induced chemokine production: linking viral replication to chemokine production in vitro and in vivo[J]. J Infect Dis. 2004,189:1419-30
[7]Alho HS, Salminen US, Maasilta PK, et al. Epithelial apoptosis in experimental obliterative airway disease after lung transplantation[J]. J Heart Lung Transplant. 2003,22:1014-22.
[8]Cooper JD, Vreim CE. NHLBI workshop summary. Biology of lung preservation for transplantation[J]. Am Rev Respir Dis. 1992,146:803-7.
[9]McCord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med. 1985,312:159-63.
[10]Al-Mehdi AB, Shuman H, Fisher AB. Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia[J]. Am J Physiol. 1997,272:294-300
[11]Ware LB, Golden JA, Finkbeiner WE, et al. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation[J]. Am J Respir Crit Care Med. 1999,159:980-8.
[12]Sugita M, Suzuki S, Kondo T, et al. Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution.Transplantation[J]. 1999,67:349-54.
[13]Yokomise H, Ueno T, Yamazaki F,et al. The effect and optimal time of administration of verapamil on lung preservation. Transplantation[J]. 1990,49:1039-43.
[14]Pickford MA, Gower JD, Dore C, et al. Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo[J]. Transplantation. 1990,50:210-8.
[15]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J].Transplantation. 1994,58:1158-62.
[16]Krishnadasan B, Naidu BV, Byrne K, et al. The role of proinflammatory cytokines in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg. 2003,125:261-72
[17]Vural KM, Oz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion[J]. Eur J Cardiothorac Surg. 2000,18:348-52.
[18]Friedenstein AJ, Gorskaja JF, Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol. 1976, 4:267-74.
[19]Caplan AI. Mesenchymal stem cells[J]. J Orthop Res. 1991 , 9:641-50.
[20]Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72
[21]Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003,100: 8407-11.
[22]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[23]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol ,2002,174 :11-20.
[24]许予明,宋波,秦洁,等.骨髓间充质干细胞对大鼠脑缺血再灌注损伤的保护机制[J ].国外医学?脑血管疾病分册,2004, 12 (9) : 657.
[25]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[26]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[27]Sch?chinger V, Erbs S, Els?sser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1210-21.
[28]Hristov M, Heussen N, Schober A, et al. Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis[J]. J Cell Mol Med, 2006, 10:727-33.
[29]Arnesen H, Lunde K, Aakhus S, et al. Cell therapy in myocardial infarction[J]. Lancet, 2007, 369: 2142-3.
[30]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: 113-21.
[31]Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (Bone marrow transfer to enhance ST-elevation infarct regeneration) trial[J]. Circulation, 2006, 113: 1287-94.
[32]Lunde K, Solheim S, Aakhus S, et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1199-209.
[33]Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium[J]. Nature, 2001, 410: 701-5.
[34]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[35]Filip S, English D, Mokry J. Issues in stem cell plasticity[J]. J Cell Mol Med, 2004, 8: 572-7.
[36]Uemura R, Xu M, Ahmad N, et al. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling[J]. Circ Res, 2006, 98: 1414-21.
[37]Gupta N, Su X, Popov B,et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice[J]. J Immunol,2007,179:1855-63.
[38]Shiraishi Y, Lee JR, Laks H, et al. Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model[J]. J Heart Lung Transplant. 1998,17:250-8.
[39]De Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation[J]. Am J Respir Crit Care Med. 2002,165:211-5.
[40]Serrick C, Adoumie R, Giaid A, et al. The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft[J]. Transplantation. 1994,58:1158-62.
[41]Fehrenbach H, Schepelmann D, Albes J M, et al. pulmonary ischemia reperfusion injury :aquantitative structure and function in isolatedheart-lungs of the rat[J]. Anat Rec. 1999,255:84-9.
[42]Tutor J D, Mason C M, Dobard E, et al. Loss of compartmen talization of alveolar tumor necrosis factor after lung injury[J]. Ann J Respi CritrCare Med. 1994,149:1107-11.
[43]Palace GP, Del Vecchio PJ, Horgan MJ, et al. Release of tumor necrosis factor after pulmonary artery occlusion and reperfusion[J]. Am Rev Respir Dis. 1993,147:143-7.
[44]Donnelly RP, Dickensheets H, Finbloom DS, et al. Interleukin-10 synergize to inhibit cell- mediated immunity in vivo[J]. J Interfon Cytokin Res. 1999,19: 563-73.
[45]Krebs DL, Hilton DJ. Complication in long-term survivors of cardiac[J]. J Cell Sci. 2000;113:2813-9.
[46]Powrie F, Menon S, Coffman RL, et al. Interleukin-4 and interleukin-10 synergize to inhibits cell-mediated immunity in vivo[J]. Eur J Immunol. 1993,23:3043-9.
[47]Fischer S, Cassivi SD, Xavier AM, et al. Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation[J]. Ann Surg. 2000,231:4242-311.
[48]Garcia Velasco JA, Arici A. Apoptosis and the pathogenesis of endometriosis[J]. Semin Reprod Med. 2003,21:165-72.
[49]Di Renzo M, Rubegni P, Sbano P, et al . ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family[J]. Arch Dermatol Res. 2003,295 :175-82.
[1]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration[J]. Circ Res, 2002, 91: 1092-102.
[2]Sch?chinger V, Erbs S, Els?sser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1210-21.
[3]Hristov M, Heussen N, Schober A, et al. Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis[J]. J Cell Mol Med, 2006, 10:727-33.
[4]Arnesen H, Lunde K, Aakhus S, et al. Cell therapy in myocardial infarction[J]. Lancet, 2007, 369: 2142-3.
[5]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: 113-21.
[6]Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (Bone marrow transfer to enhance ST-elevation infarct regeneration) trial[J]. Circulation, 2006, 113: 1287-94.
[7]Lunde K, Solheim S, Aakhus S, et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction[J]. N Engl J Med, 2006, 355: 1199-209.
[8]Zhao LR ,Duan WM,Reyes M,et al . Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats[J]. Exp Neurol ,2002 ,174:11-20.
[9]孙晓艳,陈强,赵大力,等.骨髓间充质干细胞对大鼠肝脏缺血-再灌注损伤的修复作用[J ].中国实验诊断学,2008,12(3):309-12.
[10]王共先,张中华,汪泱,等.骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响[J ] .江西医学检验,2004 ,22 (5) :387.
[11] Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003,100: 8407-11.
[12]Zhao ZQ, Corvera JS, Halkos ME, etal. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol, 2003, 285: 579-88.
[13]Argaud L, Gateau-Roesch J, Loufouat D, etal. Postconditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005, 111: 194-7.
[14]Kin H, Zhao ZQ, Sun HY, etal. Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[15]Staat P, Rioufol G, Piot C, etal. Postconditioning the human heart[J]. Circulation, 2005, 112: 2143-8.
[16]Yellon DM, Opie LH. Postconditioning for protection of the infarcting heart[J]. Lancet, 2006, 367: 456-8.
[17]Fan Q, Yang XC, Wang SY, etal. Equivalent cardioprotective effect of " half-conditioning" and postconditioning in a canine model ofmyocardial ischemia and reperfusion[J]. Zhong hua Xin Xue Guan Bing Za Zhi, 2006, 34: 363-6.
[18]Tsang A, Hausenloy DJ, MocanuMM, etal. Postconditioning: A Form of "Modified Reperfusion" Protects the Myocardium by Activating the Phosphatidylinositol 3-Kinase-Akt Pathway[J]. Circ Res, 2004, 95: 230-2.
[19]Darling CE, J iang R, Maynard M, etal. Postconditioning via stuttering reperfusion limitsmyocardial infarct size in rabbit hearts: role of ERK1 /2[J]. Am J Physiol Heart Circ Physiol, 2005, 289: 1618-26.
[20]Zatta AJ , Kin H, Lee G, etal. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signaling[J]. Cardiovasc Res, 2006, 70: 315-24.
[21]Heusch G, BuchertA, Feldhaus S, etal. No loss of cardioprotection by postconditioning in connexin 43-deficientmice[J].Basic Res Cardiol, 2006, 101: 354-6.
[1] Krause D S, Theise N D, CollectorM I, et al. Multi2organ,multi-lineage engraftment by a single bone marrow-derived stem cell[J].Cell, 2001, 105: 369-77.
[2] Pittenger M F, Mackay A M, Beck S C, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science,1999, 284: 143-7.
[3] Ortiz L A, Gambelli F,McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and meliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003, 100: 8407-11.
[4] Gross T J, Hunninghake GW. Idiopathic pulmonary fibrosis[J]. N Engl J Med, 2001, 345: 517-25.
[5] Zander D S, Cogle C R, Theise N D, et al. Donor2Derived TypeII Pneumocytes Are Rare in the Lungs of Allogeneic Hematopoietic Cell Transplant Recipients[J]. Ann Clin Lab Sci,2006, 36: 47-52.
[6] Yuehua J, Balkrishna N, Robert E, et al. Pluripotency of mesenchymal stem cells derived from adult marrow[J]. Nature,2002, 418 : 41-9.
[7] Yamada M, Kubo H, Kobayashi S, etal. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury[J]. Immunol 2004,172:1266-72.
[8] Theise N D, Henegariu O, Grove J, et al. Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow[J]. Exp Hematol, 2002, 30: 1333-8.
[9] Vintern - Johansen J, Edgerton TA, HoweHR, et al. Immediate functional recovery and avoidance of reperfusion injury with surgical revascularization of short - term coronaryocclusion[J]. Circukation, 1985, 72:431-9.
[10] Vinten - Johansen J, Buckberg GD, OkamotoF, et al. Superiority of surgical versus medical reperfusion after regional ischemia[J].Thorac Cardiovasc Surg, 1986, 92: 525-34.
[11] Okamoto F, Allen BS, Buckberg GD, et al.Reperfusion conditions: importance of ensuringgentle versus sudden reperfusion during relief of coronary occlusion[J]. Thorac Cardiovas Surg, 1986, 92: 613-20.
[12] Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J].Physiol Heart Circ Physiol, 2003, 285: 579-88.
[13] Shliakhto EV, GalagudzaMM, SyrenskiiAV,et al. Ischemic postconditioning of the myocardium: a new method of heart protection against reperfusion damage[J]. Ter Arkh, 2005,77: 77 -80.
[14] Patrick S, Gilles R, Christophe P, et al.Postconditioning the human heart[J]. Circulation, 2005, 112: 2077-8.
[15]范谦,杨新春,王树岩,等.“渐处理”降低了犬心肌缺血/再灌注损伤[ J ].中华心血管病杂志, 2006, 34: 363-6.
[16] Kin H,Zhao ZQ,Sun HY,et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004,62:74-85.
[17] Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62: 74-85.
[18] Yang XM, Proctor JB, Cui L, et al. Multip le, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. Am Coll Cardiol, 2004, 44: 1103-10.
[19] Fan Q, Yang XC, Wang SY, etal. Equivalent cardioprotective effect of " half-conditioning" and postconditioning in a canine model ofmyocardial ischemia and reperfusion[J]. Zhong hua Xin Xue Guan Bing Za Zhi, 2006, 34: 363-6.
[20]Tsang A, Hausenloy DJ, MocanuMM, etal. Postconditioning: A Form of "Modified Reperfusion" Protects the Myocardium by Activating the Phosphatidylinositol 3-Kinase-Akt Pathway[J]. Circ Res, 2004, 95: 230-2.
[21]Darling CE, J iang R, Maynard M, etal. Postconditioning via stuttering reperfusion limitsmyocardial infarct size in rabbit hearts: role of ERK1 /2[J]. Am J Physiol Heart Circ Physiol, 2005, 289: 1618-26.
[22]Zatta AJ , Kin H, Lee G, etal. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signaling[J]. Cardiovasc Res, 2006, 70: 315-24.
[23]Heusch G, BuchertA, Feldhaus S, etal. No loss of cardioprotection by postconditioning in connexin 43-deficientmice[J].Basic Res Cardiol, 2006, 101: 354-6.
[24] Kirk JB, Clquhoun IW, Dark JH, et al. Lung preservation: a review of current practice and future directions[J]. Ann Thorac Surg, 1993, 56:990-1000.
[25] Shiraishi Y, Lee JR, Laks H, et al. Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model[J]. J Heart Lung Transplant, 1998, 17:250-8.
[26] Uthoff K, Zehr KJ, Lee PC, et al. Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation[J]. Ann Thorac Surg, 1995, 59:7-13.
[27] Eppinger MJ, Jones ML, Deeb GM. Pattern of injury and role of neutrophils in reperfusion injury and role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58:713-8.
[28] Gee MH, Albertine KH. Neutrophil-endothelial cell interactions in the lung[J]. Ann Rev Physiol, 1993,55:227-48.
[27] Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia reperfusion andcirculatory shock[J].. Ann Rev Pharmacol Toxicol, 1993, 33:71-90.
[29] Cretani B, Cornillet P, Dehoux M. Alveolar type II epithelial cells produce interleukin-6 in vitro and in vivo: regulation by alveolar macrophage secretoty products[J]. J Clin Invest,1994, 94:731-40.
[30] Novick RJ, Gehman KE, Ali IS, et all. Lung preservation: the importance of endothelial and alveolar type II cell integrity[J]. Ann Thorac Surg, 1996, 62:302-14.
[31] Pinsky DJ, Naka Y, chowdhury NC, et al. The nitric oxide/cyclic GMP pathway in organ transplantation:critical role in successful lung preservation[J]. Proc Natl Acad Sci, 1994, 94:731-40.
[32] Omote Y, Ikeda K, Yamazaki K, et al. The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation[J]. Surg Today, 1994, 24:616-20.
[33] Haniuda M ,Dresler CM ,Mizuta T ,et al .Free radical mediated vascular injury in lungs preserved at moderate hypo thermia [J].Ann Thorac Surg ,1995,60:1376-81.
[34] Fisher AJ,Donnelly SC, Hirani N ,et al.Elevated levels of inter- leukin- 8 in donor lungs is associated with early graft failure after lung transplantation[J]. Am J Respir Crit Care Med ,2001,163:259-65.
[35] Rabb H , Daniels F ,O'Donnell M ,et al .Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice[J]. Am J physiol ,2000,279: 525-31.
[36] Hausen B ,Bahra M ,Mueller P ,et al .Donor pretreatment with amboxol or dexamethasone fails to ameliorate reperfusion injury in experimental lung transplantation[J].Transplant,1998,11:186-94.
[37] McRacKM.Pulmonary transplantation[J].Curr Opin Anesthesiol,2000,13:53-9.
[38] Chiang CH ,WU K,Yu CP,et al.Hypothermia and PGEL produce synergistic attenuation of ischemia-reperfusion lung injury[J] .Am J Respir Crit Care Med ,1999,160:1319-23.
[39] Lockinger A ,Schutte H,Walmrath D ,et al .Protection against gas exchange abnormalities by pre-aerosolized PGE1, iloprost and nitroprusside in lung ischemia-reperfusion[J]. Transplantation,2001,71:185-93.
[40] Featherstone RL,Chamber DJ,Kelly FJ, et al.Ischemic preconditioning enhances recovery of isolated rat lungs after hypothermic preservation[J]. Ann Thorac Surg, 2000,69:237-42.
[41] Marber MS,Latchman DS,Walker JM et al.Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction[J]. Circulation,1993,88:1264-72.
[42] Nozawa Y,Miura T,Tsuchida A, et al.Chronic treatment with an ACE inhibitor,temocapril,lowers the threshold for the infarct size-limiting effect of ischemic preconditioning[J]. Cardiovasc Drugs Ther, 1999,13:151-7.
[43] Gho BC, Shoemaker RG,van den Doel MA et al. Myocardial protection by brief ischemia in noncardiac tissue[J]. Circulation, 1996,94:2193-200.
[44] Li G,chen S,Lou W, et al. The protective effects of cardiac ischemic preconditioning on lung in cardiac operation with cardiopulmonary bypass[J].Hunan Yi Ke Da Xue Xue Bao. 1998,23:41-3.
[45] Li G,Chen S,Lu E, et al. Protective effects of ischemic preconditioning on lung ischemia reperfusion injury: an in-vivo rabbit study[J]. Thorac Cardiovasc Surg, 1999,47:38-41.
[46] Luo W, Cheng S,Jiang H,et al. Effects of ischemic preconditioning on protection of canine donor lung[J].Hunan Yi Ke Da Xue Xue Bao. 1997,22:195-8.
[47] Li G, chen S,Lou W, et al. Protective effects of ischemic preconditioning on donor lung in canine lung transplantation[J]. Chest, 1998,113:1356-9.
[48] Soncul H,Oz E,Kalaycioglu S, et al. Protective effects of ischemic preconditioning on donor lung in canine lung transplantation[J]. Chest, 1999,115:1672-7.
[49] Gasparri RI,Jannis NC,Flameng WJ, et al. Ischemic preconditioning enhances donor lung preservation in the rabbit[J].Eur J Cardiothorac Surg. 1999,16:639-46.
[50] Luo W, Cheng S,Jiang H,et al. Effect of ischemic preconditioning on adenine nucleotide levels of graft lung from canine donor[J].Hunan Yi Ke Da Xue Xue Bao.1997,22:8-10.
[51] Du ZY, Hicks M, Winlaw D, Spratt P, Macdonald P. Ischemic precon- ditioning enhances donor lung preservation in the rat[J]. J Heart Lung Transplant, 1996 ,15:1258.
[52] Yellon DM, Alkliulaifi AM, Piigsley WB. Preconditioning the humanmyocardium[J]. Lancet, 1993,34:227.
[53] Li GH,Chen SX,Lou WH,Lu EX.Protective effect of ischemic preconditioning on donor lung in the canine lung transplatation[J].Chest,1998,1:1356.
[54] Cassivi SD,Liu M ,Boehler A ,et al.Transplant immunosuppression increases and prolongs transgene expression following adenoviralmediated of rat lungs [J].J Heart Lung Transplant ,2000,19:984-94.
[55] De Perrot M ,Fischer S ,Liu M ,et al. Transtracheal administracheal administration ofadenoviral-mediated human IL-10 gene to rat donpr lungs : timing of transfection and roie of early inflammation on posttransplant graft function[J] .Mol Ther ,2001,3:258.
[56] Boasquevisque CH,Mora BN,Bernstein M,Osburn WO,Nietupski J,Scheule RK,Cooper JD,Botney M,Patterson GA.Ex vovo liposome-mediated gene transfer to lung isografts[J].J Thorac Cardiovasc Surg.1998,115:38-44.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |