益气活血中药对介入后急性冠脉综合征长期预后的影响
|
摘要
第一部分益气活血中药对介入后急性冠脉综合征长期预后的影响
目的：观察益气活血中药干预对介入(percutaneous coronary intervention, PCI)后急性冠脉综合征(acute coronary syndrome, ACS)长期预后的影响,并分析影响预后的相关因素。
方法：在前期多中心、区组随机、平行对照“中西医综合干预介入后急性冠脉综合征临床研究”的1年临床研究基础上,对2008年7月至2009年9月在京沪地区8家医院住院的702例PCI后ACS患者,进行长期随访观察。其中对照组(n=351)接受西医常规治疗,治疗组(n=351)接受益气活血中药(心悦胶囊+复方川芎胶囊)联合西医常规治疗,并分别于2011年9月-12月进行门诊和(或)电话随访。随访观察内容包括患者主要终点事件、次要终点事件及联合终点事件发生情况。主要终点事件包括心源性死亡、非致死性心肌梗死、再次血运重建(介入治疗及冠状动脉旁路移植术)；次要终点事件包括因ACS再入院、心功能不全、非致死性脑卒中及其他血栓并发症(支架内再狭窄、下肢动脉闭塞等)；联合终点事件定义为主要终点事件+次要终点事件。预后影响因素分析采用Cox比例风险模型,以终点事件作为结局变量,以终点发生事件时间为时间变量,将可能影响预后的因素纳入模型,分析影响PCI后ACS预后的相关因素及其影响程度。
结果：完成随访患者621例(88.59%),失访患者80例(11.41%),其中治疗组失访41例(11.68%),对照组失访39例(11.14%),平均随访时间为35.4±3.8个月。治疗组发生主要终点事件20例(5.70%),对照组发生主要终点事件38例(10.86%),治疗组发生主要终点事件的危险是对照组的0.53倍[RR：0.53,95%CI(0.30,0.88),P=0.013],较对照组绝对降低了5.20%[ARR：-0.052,95%CI(-0.06,-0.01)]；治疗组发生次要终点事件21例(5.98%),对照组发生次要终点事件36例(10.28%),治疗组发生次要终点事件的危险是对照组的0.58倍[RR：0.58,95%CI(0.33,0.97),P=0.037],较对照组绝对降低了4.30%[ARR：-0.043,95%CI(-0.06,-0.01)]；治疗组发生联合终点事件(主要终点+次要终点)41例,终点事件发生率为11.68%,对照组发生联合终点事件74例,发生率为21.14%。治疗组发生联合终点事件的危险是对照组的0.55倍[RR：0.55,95%CI(0.36,0.76),P=0.001],较对照组绝对降低了9.46%[ARR：-0.095,95%CI(-0.11,-0.03)]。
Cox比例风险模型分析影响预后相关因素,结果显示：在西医常规治疗基础上加益气活血干预与主要终点事件、次要终点事件、联合终点事件发生呈负相关(B=-0.69,P=0.014；B=-0.54,P=0.049；B=-0.66,P=0.001)；累及血管支数、纳入时生存质量得分与主要终点事件发生呈负相关(B=-0.79,P=0.024；B=-1.35,P=0.026)；左心室舒张末期前后径、高血压病史、高血脂病史与联合终点事件发生呈正相关(B=0.04,P=0.038；B=0.45,P=0.034；B=0.55,P=0.007)；纳入时生存质量得分与联合终点事件的发生呈负相关(B=-1.44,P=0.002)。
结论：益气活血中药联合西医常规治疗干预PCI后ACS,可明显减少不良心血管事件发生的风险；高血压病史、高血脂病史、低生存质量、左室舒张末期内径扩大、冠脉多支病变是PCI后ACS不良心血管事件发生的独立影响因素。
第二部分益气活血中药对大鼠急性心肌梗死后早期心室重构的影响
目的：观察益气活血中药对大鼠急性心肌梗死(acute myocardial infarction,AMI)后早期心室重构的影响,并从细胞外基质代谢方面探讨可能的机制。
方法：结扎大鼠冠状动脉前降支造成AMI模型。将90只造模成功的Wistar大鼠随机分为6组,每组15只,分别为假手术组(冠脉仅穿线不结扎)、模型组、西药组(缬沙坦)、益气组(西洋参茎叶总皂苷)、活血组(赤芍总苷)、益气活血组(西洋参茎叶总皂苷配伍赤芍总苷),各给药组连续灌胃给药4周,假手术组和模型组灌胃等剂量蒸馏水。超声心动图检查心脏结构及心功能变化、HE染色观察心肌组织病理变化,放射性免疫法检测各组大鼠血清肌钙蛋白T(cTnT)B型钠尿肽(BNP)、炎性因子肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、心肌纤维化因子层粘连蛋白(LN)、透明质酸(HA)、Ⅲ型前胶原氨端肽(PⅢNP)含量及心肌组织中血管紧张素Ⅲ(Ang Ⅱ)、醛固酮(ALD)、组织生长因子β1(TGF-β1)的含量。免疫组织化学染色法半定量检测各组大鼠心肌组织基质胶原Ⅰ、胶原Ⅲ、金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制剂1(TIMP-1)、骨桥蛋白(OPN)、腱糖蛋白C(TN-C)的表达水平。
结果：灌胃4周后取材,与模型组比较：(1)益气活血组大鼠心肌细胞炎性浸润减少,心肌纤维间隙水肿和心肌纤维细胞坏死变性明显减轻；(2)西药组、活血组和益气活血组心脏左室舒张末内径明显减小(P<0.05),左室射血分数明显提高(P<0.05),益气活血组室间隔收缩和舒张末期厚度明显增加(P<0.05),血清BNP水平明显下降(P<0.05)；(3)西药组、活血组和益气活血组血清炎性因子TNF-α和IL-1β的含量明显降低(P<0.05,P<0.01)；(4)各给药组心肌组织神经内分泌因子AngⅡ、ALD、TGF-β1的含量明显降低(P<0.05,P<0.01)；(5)活血组和益气活血组血清纤维化因子LN、HA、PⅢNP含量明显降低(P<0.05)；(6)西药组和益气活血组心肌组织胶原Ⅰ、胶原Ⅲ表达明显降低(P<0.05,P<0.01)；(7)活血组和益气活血组心肌组织MMP-9表达明显降低(P<0.01)、TIMP-1表达明显增高(P<0.05),MMP-9/TIMP-1比值明显降低(P<0.01)；(8)活血组和益气活血组心肌组织OPN、TN-C表达明显降低(P<0.05,P<0.01)。
结论：(1)益气活血中药(西洋参茎叶总皂苷配伍赤芍总苷)可改善大鼠AMI后的早期心室重构,改善心功能,其机制可能涉及抑制炎症反应、降低神经内分泌因子的激活、调节细胞外基质代谢有关；(2)益气活血中药通过调节胶原代谢、基质金属蛋白酶、骨桥蛋白、腱糖蛋白等影响细胞外基质构成的关键蛋白表达水平,抑制AMI后的早期心室重构。
Part1Long-Term Clinical Outcome of Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention Treated with Chinese Herbs for Supplementing Qi and Activating Blood Circulation
Objective:To investigate the long-term clinical outcome of patients with acute coronary syndrome after percutaneous coronary intervention (PCI) treated with Chinese herbs for supplementing qi and activating blood circulation (SQABC), and analyze the relative factors which affect the prognosis of patients with ACS after PCI.
Methods:The present study was based on the clinical study of "Combination of Chinese Herbal Medicines and Standard Treatment versus Standard Treatment Alone on Acute Coronary Syndrome after Percutaneous Coronary Intervention". The former study is a multicenter, randomized parallel controlled clinical trial with one-year clinical follow-up. In our study,702ACS patients who were hospitalized in8Beijing and Shanghai hospitals from July2008to September2009were enrolled The control group received standard therapy according to the guideline of Western medicine, the treatment group received standard therapy in combination with Chinese herbs of SQABC (Xinyue Capsule and Fufang Chuanxiong Capsule), with351patients in each group. Telephone and clinic follow-up was performed to recognize the main adverse cardiac events (MACEs) in the last three months in2011. The MACEs consisted of primary end point, secondary end point and combined end point. The primary end point was the composite of cardiac death, nonfatal recurrent myocardial infarction or repeat revascularization (PCI and CABG). The secondary end point was the composite of readmission for acute coronary syndrome, nonfatal cerebrovascular diseases, congestive heart failure, or other thrombus diseases (restenosis and lower extremity arterial occlusion). Combined end point consisted of primary and secondary end point. The relative factors which affected the prognostic outcome of ACS were analyzed using Cox proportional hazards model. Using end point events as outcome variable and events occurring time as time variable. The possible factors which would affect the prognostic were applied in the model to analyze the relative factors and their influence degree on ACS after PCI.
Results:621(88.59%) patients accomplished the follow-up,80(11.41%) were lost (41cases in treatment group vs.39cases in control group), the average follow-up time was35.4±3.8months.20(5.70%) cases occurred primary end point in treatment group vs.38(10.86%) in control group. Compared with control group, the primary end point occurring risk of the treatment group was0.53fold [RR,0.53;95%CI (0.30to0.88); P=0.013] and occurring rate decreased5.20%[ARR,-0.052;95%CI (-0.06to-0.01)] in treatment group.21(5.98%) cases occurred secondary end point in treatment group vs.36(10.28%) in control group. Compared with control group, the secondary end point occurring risk of treatment group was0.58fold [RR,0.58;95%CI (0.33to0.97); P=0.037] and occurring rate decreased4.30%[ARR,-0.043;95%CI (-0.06to-0.01)] in treatment group.41(11.68%) cases occurred combined end point in treatment group vs.74(21.14%) in control group. Compared with control group, the combined end point occurring risk of treatment group was0.55fold [RR,0.55;95%CI (0.36to0.76); P=0.001] and occurring rate decreased9.46%[ARR,-0.095;95%CI (-0.11to-0.03)] in treatment group.
The relative factors affecting prognostic clinical outcome were analyzed using Cox proportional hazards model. The results showed that the intervention negatively correlated with the primary end point (B=-0.69, P=0.014). Involving vessels amount negatively correlated with the primary end point (B=-0.79, P=0.024). Enrolling Life quality score negatively correlated with the primary end point (B=-1.35, P=0.026). Intervention negatively correlated with the secondary end point (B=-0.54, P=0.049). Intervention negatively correlated with the combined end point (B=-0.66, P=0.001). Left ventricular end diastole diameter positively correlated with the combined end point (B=0.04, P=0.038). Enrolling life quality score negatively con-elated with the combined end point (B=-1.44, P=0.002). The history of hypertensive disease positively correlated with the combined end point (B=0.45, P=0.034). The history of hyperlipemia disease positively correlated with the combined end point (B=0.55, P=0.007).
Conclusion:The application of Chinese herbs of SQABC in combination with Western medicine standard therapy can significantly reduce the occurrence of cardiovascular adverse events and improve the long term prognostic outcome. Hypertension, hyperlipemia, low life quality score, increased left ventricular end diastole diameter are the independent risk factors affecting the occurrence of cardiovascular adverse events in ACS after PCI.
Part2Effect of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Ventricular Remodeling of Rats with Acute Myocardial Infarction
Objective:To investigate the effect of Chinese herbs for SQABC on prophase ventricular remodeling (VR) after acute myocardial infarction (AMI) in rats and explore the possible mechanism on extracellular matrix (ECM) metabolism.
Methods:The AMI model was established by ligating the left anterior descending coronary artery of rats to induce myocardial infarction.90Wistar rats with model establishment were randomly divided into6groups,15rats in eachgroup. They were sham group (the suture was penetrated around the left anterior descending coronary artery, but not tied), model group, western medicine (WM) group of which Valsartan was administered, supplementing qi (SQ) group of which Panas quinquefolium saponin was given, activating blood circulation (ABC) group of which red peony root saponin was given, supplementing qi and nourishing yin (SQABC) group of which both Panas quinquefolium saponin and red peony root saponin were given. All of the medicine were given by gavage, both sham group and model group were administered of equivalent distilled water. After continuous intragastric administration of4weeks, ultrasonic cardiography was used to examine the morphologic change and heart function. HE staining was used to observe the myocardial pathological change. Serum levels of B-type natriuretic peptide (BNP), cardiac troponin T (cTnT), inflammation factors of tumor necrosis factor-alpha (TNF-a), interleukin-1β (IL-1β), myocardial fibrosis factors laminin (LN), hexadecenoic acid (HA), type III procollagen (PIIINP) were tested by radioimmunoassay method. Myocardium contents of angiotensin II (Ang II), aldosterone (ALD) and tissue growth factor-β1(TGF-β1) were tested by radioimmunoassay method. The protein expression of collagen I, collagen III, matrix metalloproteinases-9(MMP-9), tissue inhibitor of metalloproteinases-1(TIMP-1), osteopontin (OPN) and tenascin-C (TN-C) in myocardial tissue were tested semiquantitatively by immunohistochemical method.
Results:After4weeks, compared with model group:(1) Myocardial pathological changes of inflammatory infiltration in cardiac myocyte, edema in cardiac muscle fiber interspace and necrosis in myocardial fibrocyte obviously attenuated in SQABC group.(2) ultrasonic cardiography detection showed that in WM group, ABC group, and SQABC group left ventricular end-systole dimension reduced significantly (P<0.05), while left ventricular ejection fraction increased significantly (P<0.05). Both interventricular septum end-diastole thickness and interventricular septum end-systole thickness increased significantly in SQABC group (P<0.05). The serum level of myocardial damage marker BNP obviously deceased in SQABC group (P<0.05).(3) Serum levels of inflammation factors of TNF-α, IL-β decreased significantly in WM group, ABC group and SQABC group (P<0.05, P<0.01).(4) Myocardial tissue contents of Ang II, ALD and TGF-β1decreased significantly in each administration group (P＜0.05, P＜0.01).(5) Serum levels of myocardial fibrosis factors LN, HA, PIIINP decreased significantly in WM group, ABC group, and SQABC group (P<0.05).(6) The myocardium protein expression of collagen I and collagen III decreased significantly in WM group and SQABC group (P<0.05, P＜0.01).(7) The myocardium protein expression of OPN、TN-C decreased significantly in ABC group and SQABC group (P<0.05, P<0.01).(8)The myocardium protein expression of MMP-9decreased significantly (P＜0.01), TIMP-1increased significantly (P＜0.05), and the ratio of MMP-9/TIMP-1decreased significantly (P＜0.01) in ABC group and SQABC group.
Conclusion:(1) Chinese herbs of SQABC can improve the heart function by attenuating the prophase VR of rats after AMI. The possible mechanism of the improvement is that SQABC can inhibit the inflammation reaction, attenuate the activation of neuroendocrine factors and regulate the ECM metabolism.(2) Chinese herbs of SQABC can inhibit prophase VR and improve heart function significantly by regulating the important protein expression of collagen metabolism, MMPS, OPN, and TN-C which influence the ECM structure.
目的：观察益气活血中药干预对介入(percutaneous coronary intervention, PCI)后急性冠脉综合征(acute coronary syndrome, ACS)长期预后的影响,并分析影响预后的相关因素。
方法：在前期多中心、区组随机、平行对照“中西医综合干预介入后急性冠脉综合征临床研究”的1年临床研究基础上,对2008年7月至2009年9月在京沪地区8家医院住院的702例PCI后ACS患者,进行长期随访观察。其中对照组(n=351)接受西医常规治疗,治疗组(n=351)接受益气活血中药(心悦胶囊+复方川芎胶囊)联合西医常规治疗,并分别于2011年9月-12月进行门诊和(或)电话随访。随访观察内容包括患者主要终点事件、次要终点事件及联合终点事件发生情况。主要终点事件包括心源性死亡、非致死性心肌梗死、再次血运重建(介入治疗及冠状动脉旁路移植术)；次要终点事件包括因ACS再入院、心功能不全、非致死性脑卒中及其他血栓并发症(支架内再狭窄、下肢动脉闭塞等)；联合终点事件定义为主要终点事件+次要终点事件。预后影响因素分析采用Cox比例风险模型,以终点事件作为结局变量,以终点发生事件时间为时间变量,将可能影响预后的因素纳入模型,分析影响PCI后ACS预后的相关因素及其影响程度。
结果：完成随访患者621例(88.59%),失访患者80例(11.41%),其中治疗组失访41例(11.68%),对照组失访39例(11.14%),平均随访时间为35.4±3.8个月。治疗组发生主要终点事件20例(5.70%),对照组发生主要终点事件38例(10.86%),治疗组发生主要终点事件的危险是对照组的0.53倍[RR：0.53,95%CI(0.30,0.88),P=0.013],较对照组绝对降低了5.20%[ARR：-0.052,95%CI(-0.06,-0.01)]；治疗组发生次要终点事件21例(5.98%),对照组发生次要终点事件36例(10.28%),治疗组发生次要终点事件的危险是对照组的0.58倍[RR：0.58,95%CI(0.33,0.97),P=0.037],较对照组绝对降低了4.30%[ARR：-0.043,95%CI(-0.06,-0.01)]；治疗组发生联合终点事件(主要终点+次要终点)41例,终点事件发生率为11.68%,对照组发生联合终点事件74例,发生率为21.14%。治疗组发生联合终点事件的危险是对照组的0.55倍[RR：0.55,95%CI(0.36,0.76),P=0.001],较对照组绝对降低了9.46%[ARR：-0.095,95%CI(-0.11,-0.03)]。
Cox比例风险模型分析影响预后相关因素,结果显示：在西医常规治疗基础上加益气活血干预与主要终点事件、次要终点事件、联合终点事件发生呈负相关(B=-0.69,P=0.014；B=-0.54,P=0.049；B=-0.66,P=0.001)；累及血管支数、纳入时生存质量得分与主要终点事件发生呈负相关(B=-0.79,P=0.024；B=-1.35,P=0.026)；左心室舒张末期前后径、高血压病史、高血脂病史与联合终点事件发生呈正相关(B=0.04,P=0.038；B=0.45,P=0.034；B=0.55,P=0.007)；纳入时生存质量得分与联合终点事件的发生呈负相关(B=-1.44,P=0.002)。
结论：益气活血中药联合西医常规治疗干预PCI后ACS,可明显减少不良心血管事件发生的风险；高血压病史、高血脂病史、低生存质量、左室舒张末期内径扩大、冠脉多支病变是PCI后ACS不良心血管事件发生的独立影响因素。
第二部分益气活血中药对大鼠急性心肌梗死后早期心室重构的影响
目的：观察益气活血中药对大鼠急性心肌梗死(acute myocardial infarction,AMI)后早期心室重构的影响,并从细胞外基质代谢方面探讨可能的机制。
方法：结扎大鼠冠状动脉前降支造成AMI模型。将90只造模成功的Wistar大鼠随机分为6组,每组15只,分别为假手术组(冠脉仅穿线不结扎)、模型组、西药组(缬沙坦)、益气组(西洋参茎叶总皂苷)、活血组(赤芍总苷)、益气活血组(西洋参茎叶总皂苷配伍赤芍总苷),各给药组连续灌胃给药4周,假手术组和模型组灌胃等剂量蒸馏水。超声心动图检查心脏结构及心功能变化、HE染色观察心肌组织病理变化,放射性免疫法检测各组大鼠血清肌钙蛋白T(cTnT)B型钠尿肽(BNP)、炎性因子肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、心肌纤维化因子层粘连蛋白(LN)、透明质酸(HA)、Ⅲ型前胶原氨端肽(PⅢNP)含量及心肌组织中血管紧张素Ⅲ(Ang Ⅱ)、醛固酮(ALD)、组织生长因子β1(TGF-β1)的含量。免疫组织化学染色法半定量检测各组大鼠心肌组织基质胶原Ⅰ、胶原Ⅲ、金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制剂1(TIMP-1)、骨桥蛋白(OPN)、腱糖蛋白C(TN-C)的表达水平。
结果：灌胃4周后取材,与模型组比较：(1)益气活血组大鼠心肌细胞炎性浸润减少,心肌纤维间隙水肿和心肌纤维细胞坏死变性明显减轻；(2)西药组、活血组和益气活血组心脏左室舒张末内径明显减小(P<0.05),左室射血分数明显提高(P<0.05),益气活血组室间隔收缩和舒张末期厚度明显增加(P<0.05),血清BNP水平明显下降(P<0.05)；(3)西药组、活血组和益气活血组血清炎性因子TNF-α和IL-1β的含量明显降低(P<0.05,P<0.01)；(4)各给药组心肌组织神经内分泌因子AngⅡ、ALD、TGF-β1的含量明显降低(P<0.05,P<0.01)；(5)活血组和益气活血组血清纤维化因子LN、HA、PⅢNP含量明显降低(P<0.05)；(6)西药组和益气活血组心肌组织胶原Ⅰ、胶原Ⅲ表达明显降低(P<0.05,P<0.01)；(7)活血组和益气活血组心肌组织MMP-9表达明显降低(P<0.01)、TIMP-1表达明显增高(P<0.05),MMP-9/TIMP-1比值明显降低(P<0.01)；(8)活血组和益气活血组心肌组织OPN、TN-C表达明显降低(P<0.05,P<0.01)。
结论：(1)益气活血中药(西洋参茎叶总皂苷配伍赤芍总苷)可改善大鼠AMI后的早期心室重构,改善心功能,其机制可能涉及抑制炎症反应、降低神经内分泌因子的激活、调节细胞外基质代谢有关；(2)益气活血中药通过调节胶原代谢、基质金属蛋白酶、骨桥蛋白、腱糖蛋白等影响细胞外基质构成的关键蛋白表达水平,抑制AMI后的早期心室重构。
Part1Long-Term Clinical Outcome of Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention Treated with Chinese Herbs for Supplementing Qi and Activating Blood Circulation
Objective:To investigate the long-term clinical outcome of patients with acute coronary syndrome after percutaneous coronary intervention (PCI) treated with Chinese herbs for supplementing qi and activating blood circulation (SQABC), and analyze the relative factors which affect the prognosis of patients with ACS after PCI.
Methods:The present study was based on the clinical study of "Combination of Chinese Herbal Medicines and Standard Treatment versus Standard Treatment Alone on Acute Coronary Syndrome after Percutaneous Coronary Intervention". The former study is a multicenter, randomized parallel controlled clinical trial with one-year clinical follow-up. In our study,702ACS patients who were hospitalized in8Beijing and Shanghai hospitals from July2008to September2009were enrolled The control group received standard therapy according to the guideline of Western medicine, the treatment group received standard therapy in combination with Chinese herbs of SQABC (Xinyue Capsule and Fufang Chuanxiong Capsule), with351patients in each group. Telephone and clinic follow-up was performed to recognize the main adverse cardiac events (MACEs) in the last three months in2011. The MACEs consisted of primary end point, secondary end point and combined end point. The primary end point was the composite of cardiac death, nonfatal recurrent myocardial infarction or repeat revascularization (PCI and CABG). The secondary end point was the composite of readmission for acute coronary syndrome, nonfatal cerebrovascular diseases, congestive heart failure, or other thrombus diseases (restenosis and lower extremity arterial occlusion). Combined end point consisted of primary and secondary end point. The relative factors which affected the prognostic outcome of ACS were analyzed using Cox proportional hazards model. Using end point events as outcome variable and events occurring time as time variable. The possible factors which would affect the prognostic were applied in the model to analyze the relative factors and their influence degree on ACS after PCI.
Results:621(88.59%) patients accomplished the follow-up,80(11.41%) were lost (41cases in treatment group vs.39cases in control group), the average follow-up time was35.4±3.8months.20(5.70%) cases occurred primary end point in treatment group vs.38(10.86%) in control group. Compared with control group, the primary end point occurring risk of the treatment group was0.53fold [RR,0.53;95%CI (0.30to0.88); P=0.013] and occurring rate decreased5.20%[ARR,-0.052;95%CI (-0.06to-0.01)] in treatment group.21(5.98%) cases occurred secondary end point in treatment group vs.36(10.28%) in control group. Compared with control group, the secondary end point occurring risk of treatment group was0.58fold [RR,0.58;95%CI (0.33to0.97); P=0.037] and occurring rate decreased4.30%[ARR,-0.043;95%CI (-0.06to-0.01)] in treatment group.41(11.68%) cases occurred combined end point in treatment group vs.74(21.14%) in control group. Compared with control group, the combined end point occurring risk of treatment group was0.55fold [RR,0.55;95%CI (0.36to0.76); P=0.001] and occurring rate decreased9.46%[ARR,-0.095;95%CI (-0.11to-0.03)] in treatment group.
The relative factors affecting prognostic clinical outcome were analyzed using Cox proportional hazards model. The results showed that the intervention negatively correlated with the primary end point (B=-0.69, P=0.014). Involving vessels amount negatively correlated with the primary end point (B=-0.79, P=0.024). Enrolling Life quality score negatively correlated with the primary end point (B=-1.35, P=0.026). Intervention negatively correlated with the secondary end point (B=-0.54, P=0.049). Intervention negatively correlated with the combined end point (B=-0.66, P=0.001). Left ventricular end diastole diameter positively correlated with the combined end point (B=0.04, P=0.038). Enrolling life quality score negatively con-elated with the combined end point (B=-1.44, P=0.002). The history of hypertensive disease positively correlated with the combined end point (B=0.45, P=0.034). The history of hyperlipemia disease positively correlated with the combined end point (B=0.55, P=0.007).
Conclusion:The application of Chinese herbs of SQABC in combination with Western medicine standard therapy can significantly reduce the occurrence of cardiovascular adverse events and improve the long term prognostic outcome. Hypertension, hyperlipemia, low life quality score, increased left ventricular end diastole diameter are the independent risk factors affecting the occurrence of cardiovascular adverse events in ACS after PCI.
Part2Effect of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Ventricular Remodeling of Rats with Acute Myocardial Infarction
Objective:To investigate the effect of Chinese herbs for SQABC on prophase ventricular remodeling (VR) after acute myocardial infarction (AMI) in rats and explore the possible mechanism on extracellular matrix (ECM) metabolism.
Methods:The AMI model was established by ligating the left anterior descending coronary artery of rats to induce myocardial infarction.90Wistar rats with model establishment were randomly divided into6groups,15rats in eachgroup. They were sham group (the suture was penetrated around the left anterior descending coronary artery, but not tied), model group, western medicine (WM) group of which Valsartan was administered, supplementing qi (SQ) group of which Panas quinquefolium saponin was given, activating blood circulation (ABC) group of which red peony root saponin was given, supplementing qi and nourishing yin (SQABC) group of which both Panas quinquefolium saponin and red peony root saponin were given. All of the medicine were given by gavage, both sham group and model group were administered of equivalent distilled water. After continuous intragastric administration of4weeks, ultrasonic cardiography was used to examine the morphologic change and heart function. HE staining was used to observe the myocardial pathological change. Serum levels of B-type natriuretic peptide (BNP), cardiac troponin T (cTnT), inflammation factors of tumor necrosis factor-alpha (TNF-a), interleukin-1β (IL-1β), myocardial fibrosis factors laminin (LN), hexadecenoic acid (HA), type III procollagen (PIIINP) were tested by radioimmunoassay method. Myocardium contents of angiotensin II (Ang II), aldosterone (ALD) and tissue growth factor-β1(TGF-β1) were tested by radioimmunoassay method. The protein expression of collagen I, collagen III, matrix metalloproteinases-9(MMP-9), tissue inhibitor of metalloproteinases-1(TIMP-1), osteopontin (OPN) and tenascin-C (TN-C) in myocardial tissue were tested semiquantitatively by immunohistochemical method.
Results:After4weeks, compared with model group:(1) Myocardial pathological changes of inflammatory infiltration in cardiac myocyte, edema in cardiac muscle fiber interspace and necrosis in myocardial fibrocyte obviously attenuated in SQABC group.(2) ultrasonic cardiography detection showed that in WM group, ABC group, and SQABC group left ventricular end-systole dimension reduced significantly (P<0.05), while left ventricular ejection fraction increased significantly (P<0.05). Both interventricular septum end-diastole thickness and interventricular septum end-systole thickness increased significantly in SQABC group (P<0.05). The serum level of myocardial damage marker BNP obviously deceased in SQABC group (P<0.05).(3) Serum levels of inflammation factors of TNF-α, IL-β decreased significantly in WM group, ABC group and SQABC group (P<0.05, P<0.01).(4) Myocardial tissue contents of Ang II, ALD and TGF-β1decreased significantly in each administration group (P＜0.05, P＜0.01).(5) Serum levels of myocardial fibrosis factors LN, HA, PIIINP decreased significantly in WM group, ABC group, and SQABC group (P<0.05).(6) The myocardium protein expression of collagen I and collagen III decreased significantly in WM group and SQABC group (P<0.05, P＜0.01).(7) The myocardium protein expression of OPN、TN-C decreased significantly in ABC group and SQABC group (P<0.05, P<0.01).(8)The myocardium protein expression of MMP-9decreased significantly (P＜0.01), TIMP-1increased significantly (P＜0.05), and the ratio of MMP-9/TIMP-1decreased significantly (P＜0.01) in ABC group and SQABC group.
Conclusion:(1) Chinese herbs of SQABC can improve the heart function by attenuating the prophase VR of rats after AMI. The possible mechanism of the improvement is that SQABC can inhibit the inflammation reaction, attenuate the activation of neuroendocrine factors and regulate the ECM metabolism.(2) Chinese herbs of SQABC can inhibit prophase VR and improve heart function significantly by regulating the important protein expression of collagen metabolism, MMPS, OPN, and TN-C which influence the ECM structure.
引文
1. He J, Gu D, Wu X, et al. Major cause of death among men and women in China. N Engl J Med,2005,353:1124-1134.
2.王晓才,农一兵,林谦,等.138例冠心病患者的证候分布与组合特点分析.中医杂志,2008,49(1)：62-66.
3.周景想,唐明,李洁.2029例冠心病心绞痛中医证候特点及组合规律分析.中国中西医结合杂志,2011,31(6)：753-755.
4.肖政.127例急性冠脉综合征的中医证候回顾研究.中华实用中西医杂志,2007,7(20)：553-554.
5.王阶,何庆勇,李海霞.815例不稳定型心绞痛中医证候的因子分析.中西医结合学报,2008,6(8)：788-792.
6.周琦,尚菊菊,王玲.北京地区中医医院急性心肌梗死患者临床特征分析.中国中医急症,2011,20(1)：52-54.
7.王师菡,王阶,何庆勇,等.冠心病介入术后中医证候要素分布规律及相关因素分析.世界科学技术-中医药现代,2008,10(6)：13-15.
8.刘丛群,孙强,哀春凤.益气活血法治疗冠心病的疗效探讨.中国现代药物应用,2009,3(3)：88-89.
9.王芳芳,顾宁.益气活血法治疗冠心病心绞痛研究述.实用中医内科杂志,2009,23(1)：16-17.
10.王文波,程小燕.冠心病心绞痛有关气虚血瘀病机及其证治的研究进展.中医药导报,2007,13(12)：77-79.
11.李丹萍,陈强,易莉.益气活血法对充血性心力衰竭患者疗效和心功能的影响.中国中西医结合杂志,2006,26(6)：552-554.
12.郑峰,谢荣芳,褚剑锋,等.冠心生脉饮对冠心病心绞痛患者血清Ⅵ、GF与NO的影响.福建中医学院学报,2006,7(4)：17-18.
13.赵凡.益气活血合剂治疗冠心病不稳定型心绞痛临床疗效观察.中国中医药咨讯,2010,2(15)：251.
14.李健,张敏州,陈伯钧.通冠胶囊对冠心病介入术后气虚血瘀证患者的影响.中国中西医结合杂志,2008,28(1)：32-35.
15.工居新.益气活血汤治疗冠心病心绞痛临床观察.中西医结合心脑血管病杂志,2008,6(4)：460-461.
16.藕二祥.益气活血法对冠心病心绞痛患者血小板活化功能的影响.中国中医急症,2011,20(1)：122-123.
17.杨爱东,郭永洁,余星,等.益气活血通脉颗粒对动脉粥样硬化家兔血液流变性及血小板cAMP、cGMP的影响.中国中医药科技,2005,12(4)：221-222.
18.王宗仁,李昌军,王文,等.芪丹通脉片对缺血再灌注大鼠损伤的保护作用.中西医结合心脑血管病杂志,2007,5(9)：821-823.
19.刘国彬.益气活血汤对急性心肌缺血模型大鼠治疗作用的实验研究.海峡药学,2010,2(11)：30-33.
20.蒋跃绒,刘颖,郭春雨.芪丹液对急性心肌梗死大鼠心肌缺血损伤的影响.中西医结合心脑血管病杂志,2009,7(2)：167-169.
21.韩宁林,戴小华,周宜轩.益气活血法对心肌缺血/再灌注损伤大鼠IL-6及TNF-α含量的影响.中国中医急症,2005,14(5)：456-457.
22.黄培培,郭书文,杨蟠储.心肌缺血大鼠血清TNF-α、IL-6变化及益气活血药对其的影响.北京中医药大学学报,2010,33(9)：614-617.
23.马静,龙铟,王宗仁.益气活血复方对心肌线粒体氧自由基损伤的保护作用.心脏杂志,2006,18(2)：178-181.
24.吴爱明,张冬梅,翟建英.益气活血药对心肌梗死大鼠心脏结构和Cx43表达的影响.中西医结合心脑血管病杂志,2011,9(3)：322-324.
25.杨志霞,林谦,马利.黄芪多糖丹参酮对慢性心衰大鼠MIF表达的调控作用.中国药理学通报,2011,27(9)：1214-1217.
1.孟淑玲,宋有诚.急性心肌梗死后左心室重构及其防治.中国心血管杂志,2002,7(3)：212-214.
2. Frantz S, Bauersachs J, Ertl G, et al. Post-infarct remodelling:contribution of wound healing and inflammation. Cardiovasc Res,2009,81(3):474-481.
3. Kabe Y, Ando K, Hirao S, et al. Redox regulation of NF-kappa B activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal,2005,7(3):395-403.
4. Lu L, Chen SS, Zhang JQ, et al. Activation of nuclear factor kappa B and its proinflammatory mediator cascade in the infarcted rat heart. Biochem Biophys Res Commun,2004,321(4):879-885.
5. Nichols TC. NF-kappa B and reperfusion injury. Drug News Perspect,2004,17(2): 99-104.
6. Pechanova O, Simko F. The role of nuclear factor kappa B and nitric oxide interaction in heart remodelling. J Hypertension,2010, Suppl 1:39-44.
7. Jacobs M, Staufenberger S, Gergs U, et al. Tumor necrosis factor-alpha at acute myocardial infarction in rats and effects on cardiac fibroblasts. J Mol Cell Cardiol, 1999,31(11):1949-1959.
8. Aukrust P, Ueland T, Lien E, et al. Cytokine network in congestive heart failure secondary toischemic or idiopathic cardiomyopathy. Am J Cardiol 1999,83(3): 376-382.
9. Toshiyuki T, Toshihisa A, Tsutomu Y, et al. Serum C-reactive protein elevation in left ventricular remodeling after acute myocardial infarction role of neurohormones and cytokines. International Journal of Cardiology,2003,88(2):257-265.
10. Ohstuka T, Hamada M, Inoue K, et al. Relation of circulating interleukin 6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction. Clin Cardiol,2004,27(7):417-420.
11. Uehara K, Nomura M, Ozaki Y. High sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels, 2003,18(2):67-74.
12. Jiang Xu, Oscar A. Carretero, Chun-Xia Lin, et al. Role of cardiac overexpression of ANG Ⅱ in the regulation of cardiac function and remodeling postmyocardial infarction. Am J Physiol Heart Circ Physiol,2007,293(3):H1900-H1907.
13. Matsumoto R, Yoshiyama M, Omura T, et al. Effects of aldosterone receptor antagonist and angiotensin Ⅱ type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction.Circ J 2004,68(4): 376-382.
14. Willenheimer R. Left ventricular remodeling and dysfunction, Can the process be prevented, Int J Cardiol,2000,72(4):143-150.
15. Peng J, Gurantz D, Tran V, et al. Tumor necrosis factor-alpha induced ATI receptor upregulation enhances angiotensin Ⅱ-mediated cardiac fibroblast responses that favor fibrosis. Circ Res,2002,91(12):1119-1126.
16. Schnee JM, Hsueh WA. Angiotension Ⅱ, adhension, and cardiac fibrosis. Cardiovasc Res,2007,46(2):264-268.
17. Kawano H, Do YS, Kawano Y, et al. Angiotension Ⅱ has multiple profibrotic effects in human cardiac fibroblasts. Circulation,2009,101(10):1130-1137.
18. Frantz S,Adamek A, Wolf J, et al. Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol,2008,103(5):485-492.
19. Van Kats JP, Methot D, Paradis P, et al. Use of a biological peptide pump to study chronic peptide homone action in transgenic mice:direct and indirect effects of angiotensin Ⅱ on the heart. J Biol Chem,2009,276(47):4012-4017.
20. Brower GL, Gardner JD, Forman MF, et al. The relationship between myocardial extracellular matrix remodeling and ventricular function. Eur J Cardiothorac Surg,2006,30(4):604-610.
21. Picard F, Brehm M, Fassbach M, et al. Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP-1) and its inhibitor (TIMP-1) in DCM patients. Clin Res Cardiol,2006,95(5):261-269.
22. Spinale FG. Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function. Physiol Rev,2007,87(4):1285-1342.
23. Chen K, Chen J, Li D, et al. Angiotensin II regulation of collagen type I expression in cardiac fibroblasts:modulation by PPAR-gamma ligand pioglitazone. Hypertension,2004,44(5):655-661.
24. Boengler K, Hilfiker-Kleiner D, Drexler H, et al. The myocardial JAK/STAT pathway:from protection to failure. Pharmacol Therap,2008,120(2):172-185.
25. Chorianopoulos E, Heger T, Lutz M, et al. FGF-inducible 14-kDa protein (fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappa B activation by TWEAK. Basic Res Cardiol,2010,105(2): 301-313.
26. Rouet-Benzineb P, Gontero B. Angiotensin Ⅱ induces nuclear factor-Kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway. J Mol Cell Cardiol,2000,32(10):1767-1778.
27. Webb CS, Bonnema DD. Specific Temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction:relation to left ventricular remodeling.Circulation,2006,114(10):1020-1027.
28. Song G, Hennessy M, Zhao YL, et al. Adrenoceptor blockade alters plasma gelatinase activity in patients with heartfailure and MMP-9 promoter activity in a human cell line (ECV304). Pharmaco Res,2006,54(1):57-64.
29. Duncharme A, Frantz S, Alikawa M, et al. Targeted deletion of matrix metalloproteinase-9 atteunates left ventriclar enlargement and collagen accumulation after experimental myocardial infaction. J Clin Invest,2000,106(1): 55-62.
30. Trueblood NA, Xie Z, Communal C, et al. Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res,2010,88(10):1080-1087.
31. Yutaka Matsui, Nan Jia, Hiroshi Okamoto, et al. Role of osteopentin in cardiac fibrosis and remodeling in angiotensin II induced cardiac hypertrophy. Hypertension, 2009,43(6):1195-1201.
32.梁春,吴宗贵,丁健,等.腱糖蛋白c对大鼠腹腔巨噬细胞活性及其分泌表达基质金属蛋白酶-2,9的影响.中华心血管病杂志,2003,31(5)：365-368.
33. Imanaka-Yoshida K, Hiroe M, Nishikawa T, et al. Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during tissue remodeling after myocardial infarction. Lab Invest,2009,81(7):10-15.
34. Alves TR, da Fonseca AC, Nunes SS, et al. Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells. Exp Cell Res,2011,317(15):2073-2085.
35. Aso N, Tamura A, Nasu M. Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy. Am J Cardiol,2010,94 (11):1468-1650.
36.黄国倩,刘虹,舒先红,等.超声心动图评价粒细胞集落刺激因子动员自身骨髓干细胞对心肌梗死后左心室重构及心功能的影响.中华超声影像学杂志,2004,13(11)：848-852.
37. HusicM, Egstrup K. Usefulness of left ventricular diastolic wall motion abnormality as an early predictor of left ventricular dilation after a first acute myocardial infarction. Am J Cardio,2005,96(9):1186-1189.
38.郭薇,陈斌,王春.实时三维超声心动图对心肌梗死患者左心室重构的评价.中华临床医师杂志,2010,4(6)：752-756.
39. Chung CM, Nakamura S, Tanaka K, et al. Effect of recanalization of chronic total occlusions on global and regional left ventricular function in patients with or without previous myocardial infartion. Catheter Cardiovasc Interv,2003,60(3): 368-374.
40. Niccoli G, Cosentino N, Lombardo A, et al. Angiographic patterns of myocardial reperfusion after primary angioplasty and ventricular remodeling. Coron Artery Dis,2011,22(7):507-514.
41. Miura T, Yuda S. Are treatment effects of ACEI and ARB in post-MI patients homogeneous? Circ J,2009,73(5):820-821.
42.王振涛,王硕仁,李敏,等.活血益气注射液治疗心衰大鼠心气虚证的研究.中药药理与临床,2000,16(增刊)：73-75.
43.董国菊,刘剑刚,史大卓,等.愈心梗液对急性心肌梗死大鼠心肌能量代谢和内皮功能障碍的影响.中国中医急症,2005,14(9)：872-874.
1. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part 1. Circulation,2003, 108(14):1664-1672.
2. Kolodgie FD, Virmani R, Burke AP, et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004,90(12):1385-1391.
3. 刘华,王永武.冠心病血运重建治疗进展.同济大学学报(医学版),2003,24(4)：330-333.
4. 中华医学会心血管病学分会.不稳定性心绞痛和非ST段抬高心肌梗死诊断与治疗指南.中华心血管病杂志,2007,35(4)：295-304.
5. Armstrong, EricR Bates, Lee A Green, et al.2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. JACC,2008,51(2):210-247.
6. Tanaka A, Kawarabayashi T, Nishibori Y, et al. No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 2002, 105(18):2148-2152.
7. Resnic FS, Wainstein MW, Lee MK, et al. No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J,2003,145(1):42-46.
8. HuangY, Salu k, WangL, et al. Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine cornary model. J Invasive Cardiol,2005,17(8): 142-148.
9. Mauri L, Hsich WH, Massaro JM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med,2007,356(5):1020-1029.
10. Kentaro Ejiri, Masaharu Ishihara, Kazuoki Dai, et al. Three-Year Follow-up of Sirolimus-Eluting Stents vs. Bare Metal Stents for Acute Myocardial Infarction. Circ,2012,76(1):65-70
11. Hee-Hwa Ho, Vincent Pong; Chung-Wah Siu, et al. Long-term Clinical Outcomes of Drug-Eluting Stents vs. Bare-Metal Stents in Chinese Patients. Clin. Cardiol, 2010,33(6):E22-E29.
12. Victor M.G, Legrand Patrick, W. Serruys, et al. Three-Year Outcome After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease. Circulation,2004,109(5):1114-1120.
13. Lisette Okkels Jensen, Michael Maeng, Per Thayssen, et al. Clinical Outcome After Primary Percutaneous Coronary Intervention With Drug-Eluting and Bare Metal Stents in Patients With ST-Segment Elevation Myocardial Infarction. Circ Cardiovasc Interv,2008,1(2):176-184.
14.中医研究院西苑医院内科,东直门医院内科,广安门医院内科,北京宣武医院内科.以“抗心梗合剂”为主治疗急性心肌梗塞118例疗效分析.中华内科杂志,1976,12(4)：212-215.
15.徐浩,史大卓,陈可冀.芎芍胶囊预防冠状动脉介入治疗后再狭窄的临床研究.中国中西医结合杂志,2000,20(7)：494-497.
16.李永强,金枚,仇盛蕾,等.益气养阴活血中药对急性心肌梗死患者血运重建后心室壁运动的影响.中国中西医结合杂志,2009,29(4)：300-304.
17.王承龙,殷惠军,史大卓,等.西洋参茎叶皂苷心血管药理研究概述.中药新药与临床药理,2006,17(1)：76-78.
18.刘雪东,李伟东,蔡宝昌,等.当归化学成分及对心脑血管系统作用研究进展.南京中医药大学学报,2010,26(2)：155-157.
19.李善春,杨军,方毅民,等.川芎嗪对急性心梗死急诊冠状动脉介入治疗后“心肌无复流”的影响.中华核医学杂志,2006,26(6)：366-369.
20. J. J. Thune, J. Signorovitch, L. Kober, et al. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-riskmyocardial infarction. Hypertension 2008,51(1):48-54.
21. Rakugi H, Yu H, A. Kamitani, et al. Links between hypertension and myocardial infarction. American Heart Journal,1996,132(1):213-221.
22. D. G. Kang, M. H. Jeong, Y. Ahn, et al. Clinical effects of hypertension on the mortality of patients with acute myocardial infarction. Journal of Korean Medical Science,2009,24(5):800-806.,
23. He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet,2009,374 (97):1765-1772.
24. Schillaci G, Mannarino MR, Pucci G, et al. Age-specific relationship of aortic pulse wave velocity with left ventricular geometry and function in hypertension. Hypertension,2007,49(2):317-21.
25. Chirinos JA, Zanlbrlo JP, Chakko S, et al. Aortic Pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Circulation,2005,45(4):980-985.
26. Nissen SE, Tuzeu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure; The CAMELOT study:A randomized controlled trial. JAMA,2004,292(18): 2217-2225.
27. Madhavan S, Ooi WL, Cohen H, et al. Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction. Hypertension,1994, 23(3):395-401.
28. Pedersen SS, Versteeg H, Denollet J, et al. Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting. Qual Life Res.,2011,20(4):559-567.
29.邓艳红,董吁钢,陈丹丹,等.堪萨斯城生存质量表对慢性心力衰竭患者生存质量评估的可行性评价.中华心血管病杂志,2004,32(8)：676-679.
30. Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med.,2008,359(7):677-687.
31. Packard CJ, Ford I, Robertson M, et al. Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation,2005,112(20): 3058-3065.
32. Ichiro Matsumoto, Yuichi Miyake, Mizuki Mizukawa, et al. Impact of Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio on Long-Term Outcome in Patients Undergoing Percutaneous Coronary Intervention. Circulation Journal,2011,75(2):905-910.
33. Walldius G, Jungner I, Aastveit AH, et al. The apoB/apoAl ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med, 2004,42(12):1355-1363.
34. Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. Am Coll Cardiol,2008,51(7):724-730.
35.顾复生.对大型他汀类药物临床研究强化降脂治疗的分析.中华老年医学杂志,2008,27(8)：636-638.
36.邹凤军,丁五麟,张小杭,等.超声心动图评价急性心肌梗死后左室扩大对左室收缩功能的影响.北京医学,2005,27(6)：347-370.
37. Cohen M, Charney R, Hershma R, et al. Reversal of chronic ischemic myocardial dysfunction after transluminal coronary angioplasty. J Am Cardiol,1988,12: 1193-1198.
38.蒋利,沈卫峰,张建盛,等.多支血管病变患者冠状动脉内支架术疗效观察临床心血管病杂志,2002,18(10)：481-483.
39. Serruys PW, Unger F, Sousa JE, et al. Comparison of coronary artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med,2001, 344:1117-1124.
40.杨跃进,罗彤,高润霖,等.首次心肌梗死后择期经皮冠状动脉介入治疗的长期预后分析.中华心血管病杂志,2003,31(11)：818-821.
41. RodriguezA, Benrardi V, Navia J, et al. Argentine randomized study:Coronary angioplasty with stenting versus coronary bypass surgery in patients with multiplevessel disease (ERACI Ⅱ):30-day an done-year fllow-up results. J Am Coll Cardiol,2001,37:51-58.
1. Gregory M, Fomovsky, Stavros Thomopoulos, et al. Contribution of Extracellular Matrix to the Mechanical Propertiesof the Heart. J Mol Cell Cardiol.2009,29(3): 490-496.
2. Rogelio Zamilpa, Merry L. Lindsey. Extracellular matrix turnover and signaling during cardiac remodeling following MI:causes and consequences. J Mol Cell Cardiol.2010,48(3):558-563.
3.张松飞,王晓娜,潘涛,等.中医药对心肌缺血再灌注损伤的保护作用及机制的实验研究进展.中国中医急症,2011,20(3)：432-435.
4. Janicki J.S, Brower G.L, The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Fail.2002,8 (6 Suppl):319-325.
5.吴爱明,赵明镜,张冬梅,等.心梗后心力衰竭模型大鼠中医证候特点及心脏的超声评价.中国中西医结合杂志,2007,27(3)：227-229.
6. M.G. Sutton, N. Shaipe. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000,101(25):2981-2988.
7. Norman Sharpe. Cardiac Remodeling in Coronary Artery Disease. Am J Cardiol 2004; 93(suppl):17-20.
8. 郭薇,陈斌,王春,等.实时三维超声心动图评估心肌梗死患者的左室变化.中国超声医学杂志,2009,25(3)：281-284.
9. Litwin SE, Katz SE, Morgan JP, et al. Serial echocardiographic assessment of left ventdcular geometry and function alter large myocardial infarction in the rat. Circulation 1994,89(1):345-354.
10. Prunier F, Gaertner R, Louedec L, et al. Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats. Am J Physiol Heart Circ Physiol,2002,283(1):346-352.
11. Kazmi KA, Iqbal SP, Bakr A, et al. Admission creatine kinase as a prognostic marker in acute myocardial infarction. J Pak Med Assoc 2009,59(12):819-822.
12. Vuolteenaho O, Alakopsala M, Ruskoaho H. BNP as a biomarker in heart disease. Adv Clin Chem,2005,40 (1):1-36.
13. Eugene Braunwald. Biomarkers in Heart Failure. N Engl J Med 2008,358(20): 2148-2159.
14. Alans S, Peter A. Cardiac natfiuretic peptides:A proteomic window to cardiac function and clinical management. Rev Cardiovasc Med,2009,4(14):3-12.
15.吴学明,左志通,陈艳红,等.血浆脑利钠肽浓度与心室重构的关系.中国微循环,2007,11(3)：195-197.
1. Hutchinson Kirk R, Stewart JA Jr, Lucchesi P, et al. Extracellular matrix remodeling during the progression of volume overload-induced heart failure. Journal of Molecular and Cellular Cardiology,2010,48(3):564-569.
2. Borg TK, Baudino TA. Dynamic interactions between the cellular components of the heart and the extracellular matrix. Pflugers Arch,2011,462(1):69-74.
3. Holmes JW, Borg TK, Covell JW. Structure and mechanics of healing myocardial infarcts. Annu Rev Biomed Eng,2005,7:223-253.
4. Murtuza B, Suzuki K, Bou Gharios G, et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA,2004,101(12):4216-4221.
5. Matsumura S, Iwanaga S, Mochizuki S, et al. Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice. J Clin Invest,2005,115(3):599-609.
6. Li J, Schwimmbeck PL, Tschope C, et al. Collagen degradation in a murine myocarditis model:relevance of matrix metalloproteinase in association with inflammatory induction. Cardiovasc Res,2002,56(2):235-247.
7. Bradham WS, Bozkurt B, Gunasinghe H, et al. Tumor necrosis factor aand myocardial remodeling in progression of heart failure:a current perspective. Cardiovasc Res,2002,53(4):822-830.
8. Nakano M, Knowlton AA, Dibbs Z, et al. Tumor necrosis factor-alpha confers resistance to hypoxic injury in the adult mammalian cardiac myocyte. Circulation, 2004,97(14):1392-1400.
9. Kubota T, McTieman CF, Frye CS, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific over expression of tumor necrosis factor-alpha. Cire Res, 2007,81(4):627-635.
10.王鹏飞,刘振,刘玲玲,等.白细胞介素1p和基质蛋白酶2、基质蛋白酶9/基质蛋白抑制因子1在左室重构中的动态表达及内在联系.临床医学,2010,30(3)：96-99.
11. Johannes Lagethon Bjornstad, Ivar Sjaastad, et al. Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload. European Heart Journal,2011,32(2):236-245.
12. Deten A, Holzl A, Leicht M, et al. Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats. J Mol Cell Cardiol,2006,33(6):1191-1207.
13.赵永锋,朱文晖,唐水娟,等.心梗后大鼠应变、应变率成像及心室重塑研究.中国超声医学杂志,2011,27(4)：293-296.
14. Herpel E, Pritsch M, Koch A, et al. Interstitial fibrosis in the heart:differences in extracellular matrix proteins and matrix metalloproteinases in end-stage dilated, ischemic and valvular cardiomyopathy. Histopathology,2006,48(6):736-747.
15. Espira L, Michael PC. Emerging concepts in cardiac matrix biology. Canadian journal of physiology and pharmacology,2009,87(12):996-1008.
16. Suzuki N, Yokoyama F, Nomizu M. Functional sites in the laminin alpha chains. Connect Tissue Res,2005,46(3):142-152.
17. Sarah McCurdy, Catalin F. Baicu, Stephane Heymans, et al. Cardiac Extracellular Matrix Remodeling:Fibrillar Collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC). J Mol Cell Cardiol,2010,48(3):544-549.
18.宋颖,王丽萍,胡霞,等.急性心肌梗死后血清Ⅲ型前胶原蛋白与左室功能变化关系的临床研究.中国急救医学,2003,23(4)：274-275.
19. Moshal KS, Tyagi N, Moss V, et al. Early induction of matrix metalloproteinase-9 transducers signalling in human heart end stage failure. J Cell Mol Med,2005,9(3): 704-713.
20. Ducharme A, Frantz S, Aikawa M, et al.Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest,2000,106(7): 55-62.
21. Kalela A, Koivu TA, Sisto T, et al. Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease. Seand J Clin Lab Invest,2002, 62(5):337-342.
22. Raaf L, Noll C, Cherifi Mel H, et al. Myocardial fibrosis and TGFB expression in hyperhomocysteinemic rats. Mol Cell Biochem,2011,347(12):63-70.
23. Moore L, Fan D, Basu R, et al. Tissue inhibitor of metalloproteinases (TIMPs) in heart failure. Heart Fail Rev,2011,65(2):72-76.
24. Nagase H, Visse R, Murphy G. Structure and function of matrix metal proteinases and TIMPs. Circ Res,2006,69(3):562-573.
25. Espira L, Michael PC. Emerging concepts in cardiac matrix biology. Canadian journal of physiology and pharmacology,2009,87(12):996-1008.
26. Mahipal Singh, Cerrone R. Foster, Suman Dalal, et al. Osteopontin:role in extracellular matrix deposition and myocardial remodeling post-MI. J Mol Cell Cardiol.,2010,48(3):538-543.
27. Kruzynska-Frejtag A, MachnickiM, Rogers R, et al. Osteopontin (an osteoblast-specific factor) is expressed within the embryonic mouse heart during valve formation. Mech Dev,2004,103(2):183-188.
28.张玉玲,周淑娴,雷娟,等.血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白表达及胶原沉积的影响.中国循环杂志,2007,22(4)：307-310.
29. Kupfahl C, Pink D, Friedrich K, et al. Angiotensin Ⅱ directly increases transforming growth factor b1 and osteopontin and indirectly affects collagen mRNA expression in the human heart. Cardiovasc Res.,2000,46(4):463-475.
30. Brellier F, Tucker RP, Chiquet-Ehrismann R. Tenascins and-their implications in diseases and tissue mechanics. Scand J Med Sci Sports,2009,19(4):511-519.
31. Chiquet-Ehrismann R, Chiquet M. Tenascins:regulation and putative functions during pathological stress. J Pathol 2003,200(9):488-499.
32.赵学,钟才进,吴宗贵,等.骨桥蛋白通过促血管新生调节心肌梗死后左室重构.上海医学,2005,43(5)：301-303.
33. Fujimoto N, Onishi K, Sato A, et al. Incremental prognostic values of serum tenascin-C levels with blood B-type natriuretic peptide testing at discharge in patients with dilated cardiomyopathy and decompensated heart failure. J Card Fail., 2009,15(10):898-905.
34. Jian B, Jones PL, Li Q, et al. Matrix metalloproteinase 9 is associated with tenascin-C in calcilic aortic stenosis. Am J Path,2001,159(1):321-327.
35. Terasaki F, Okamoto H, Onishi K, et al. Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy. Circ J 2007,71(5):327-330.
36. Basso N, Cini R, Pietrelli A, et al. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol,2007,293(7):1351-1358.
37. Ikeuchi M, Tsutsui H, Shiomi T, et al. Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction. Cardiovasc Res,2004,64(6):526-535.
38. Marcin Bujak, Nikolaos G, Frangogiannis. The role of TGF-β1 Signaling in myocardial Infarction and Cardiac Remodeling. Cardiovasc Res.,2007,74(2): 184-195.
39. Teekakirikul P, Eminnga S, Toka O, et al. Cardiac fibrosis in mice with hypenrophic cardiomyopathy is mediated by nonmyocyte proliferation and requires TGF-β1 J Clin Invest,2010,120(10):3520-3529.
40. Lindholm L H. Valsartan treatment of hypertension-does value add value? Lancet, 2004,363(4):2010-2011.
41.杜广胜,邱强,马业新,等.缬沙坦对心肌缺血坏死后心肌转化生长因子-β及Ⅰ、Ⅲ型胶原表达的影响.中国急救医学,2005,25(5)：344-345.
42.王承龙,殷惠军,史大卓,等.西洋参茎叶皂苷心血管药理研究概述.中药新药与临床药理,2006,17(1)：76-78.
43.范宝晶,裴非,赵学忠,等.西洋参茎叶总皂苷对心肌肥厚大鼠血管内皮功能的影响.中国老年学杂志,2009,29(7)：811-812.
44.王承龙,史大卓,殷惠军,等.西洋参茎叶总皂苷对急性心肌梗死大鼠心肌VEGF、bFGF表达及血管新生的影响.中国中西医结合杂志,2007,27(4)：331-334.
45.刘芬,王秋静,吕文伟,等.赤芍总甙对犬急性缺血心肌的保护作用.中国临床康复,2005,9(31)：136-138.
46.孙大军,祁功才,吕文伟,等.赤芍总苷对实验性血栓形成的影响及其作用机制.中国老年学杂志,2006,26(8)：1080-1081.
47.朱慧民,祝彼得.赤芍防止高脂喂养兔颈总动脉球囊损伤术后血管狭窄的实验研究.中国中西医结合杂志,2004,24(6)：538-540.
48. Elena MV de Cavanagh, Marcelo Ferder, Felipe Inserra, et al. Angiotensin II, mitochondria, cytoskeletal and extracellular matrix connections:an integrating viewpoint. Am J Physiol Heart Circ Physiol,2009,296(3):H550-H558.
2.王晓才,农一兵,林谦,等.138例冠心病患者的证候分布与组合特点分析.中医杂志,2008,49(1)：62-66.
3.周景想,唐明,李洁.2029例冠心病心绞痛中医证候特点及组合规律分析.中国中西医结合杂志,2011,31(6)：753-755.
4.肖政.127例急性冠脉综合征的中医证候回顾研究.中华实用中西医杂志,2007,7(20)：553-554.
5.王阶,何庆勇,李海霞.815例不稳定型心绞痛中医证候的因子分析.中西医结合学报,2008,6(8)：788-792.
6.周琦,尚菊菊,王玲.北京地区中医医院急性心肌梗死患者临床特征分析.中国中医急症,2011,20(1)：52-54.
7.王师菡,王阶,何庆勇,等.冠心病介入术后中医证候要素分布规律及相关因素分析.世界科学技术-中医药现代,2008,10(6)：13-15.
8.刘丛群,孙强,哀春凤.益气活血法治疗冠心病的疗效探讨.中国现代药物应用,2009,3(3)：88-89.
9.王芳芳,顾宁.益气活血法治疗冠心病心绞痛研究述.实用中医内科杂志,2009,23(1)：16-17.
10.王文波,程小燕.冠心病心绞痛有关气虚血瘀病机及其证治的研究进展.中医药导报,2007,13(12)：77-79.
11.李丹萍,陈强,易莉.益气活血法对充血性心力衰竭患者疗效和心功能的影响.中国中西医结合杂志,2006,26(6)：552-554.
12.郑峰,谢荣芳,褚剑锋,等.冠心生脉饮对冠心病心绞痛患者血清Ⅵ、GF与NO的影响.福建中医学院学报,2006,7(4)：17-18.
13.赵凡.益气活血合剂治疗冠心病不稳定型心绞痛临床疗效观察.中国中医药咨讯,2010,2(15)：251.
14.李健,张敏州,陈伯钧.通冠胶囊对冠心病介入术后气虚血瘀证患者的影响.中国中西医结合杂志,2008,28(1)：32-35.
15.工居新.益气活血汤治疗冠心病心绞痛临床观察.中西医结合心脑血管病杂志,2008,6(4)：460-461.
16.藕二祥.益气活血法对冠心病心绞痛患者血小板活化功能的影响.中国中医急症,2011,20(1)：122-123.
17.杨爱东,郭永洁,余星,等.益气活血通脉颗粒对动脉粥样硬化家兔血液流变性及血小板cAMP、cGMP的影响.中国中医药科技,2005,12(4)：221-222.
18.王宗仁,李昌军,王文,等.芪丹通脉片对缺血再灌注大鼠损伤的保护作用.中西医结合心脑血管病杂志,2007,5(9)：821-823.
19.刘国彬.益气活血汤对急性心肌缺血模型大鼠治疗作用的实验研究.海峡药学,2010,2(11)：30-33.
20.蒋跃绒,刘颖,郭春雨.芪丹液对急性心肌梗死大鼠心肌缺血损伤的影响.中西医结合心脑血管病杂志,2009,7(2)：167-169.
21.韩宁林,戴小华,周宜轩.益气活血法对心肌缺血/再灌注损伤大鼠IL-6及TNF-α含量的影响.中国中医急症,2005,14(5)：456-457.
22.黄培培,郭书文,杨蟠储.心肌缺血大鼠血清TNF-α、IL-6变化及益气活血药对其的影响.北京中医药大学学报,2010,33(9)：614-617.
23.马静,龙铟,王宗仁.益气活血复方对心肌线粒体氧自由基损伤的保护作用.心脏杂志,2006,18(2)：178-181.
24.吴爱明,张冬梅,翟建英.益气活血药对心肌梗死大鼠心脏结构和Cx43表达的影响.中西医结合心脑血管病杂志,2011,9(3)：322-324.
25.杨志霞,林谦,马利.黄芪多糖丹参酮对慢性心衰大鼠MIF表达的调控作用.中国药理学通报,2011,27(9)：1214-1217.
1.孟淑玲,宋有诚.急性心肌梗死后左心室重构及其防治.中国心血管杂志,2002,7(3)：212-214.
2. Frantz S, Bauersachs J, Ertl G, et al. Post-infarct remodelling:contribution of wound healing and inflammation. Cardiovasc Res,2009,81(3):474-481.
3. Kabe Y, Ando K, Hirao S, et al. Redox regulation of NF-kappa B activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal,2005,7(3):395-403.
4. Lu L, Chen SS, Zhang JQ, et al. Activation of nuclear factor kappa B and its proinflammatory mediator cascade in the infarcted rat heart. Biochem Biophys Res Commun,2004,321(4):879-885.
5. Nichols TC. NF-kappa B and reperfusion injury. Drug News Perspect,2004,17(2): 99-104.
6. Pechanova O, Simko F. The role of nuclear factor kappa B and nitric oxide interaction in heart remodelling. J Hypertension,2010, Suppl 1:39-44.
7. Jacobs M, Staufenberger S, Gergs U, et al. Tumor necrosis factor-alpha at acute myocardial infarction in rats and effects on cardiac fibroblasts. J Mol Cell Cardiol, 1999,31(11):1949-1959.
8. Aukrust P, Ueland T, Lien E, et al. Cytokine network in congestive heart failure secondary toischemic or idiopathic cardiomyopathy. Am J Cardiol 1999,83(3): 376-382.
9. Toshiyuki T, Toshihisa A, Tsutomu Y, et al. Serum C-reactive protein elevation in left ventricular remodeling after acute myocardial infarction role of neurohormones and cytokines. International Journal of Cardiology,2003,88(2):257-265.
10. Ohstuka T, Hamada M, Inoue K, et al. Relation of circulating interleukin 6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction. Clin Cardiol,2004,27(7):417-420.
11. Uehara K, Nomura M, Ozaki Y. High sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels, 2003,18(2):67-74.
12. Jiang Xu, Oscar A. Carretero, Chun-Xia Lin, et al. Role of cardiac overexpression of ANG Ⅱ in the regulation of cardiac function and remodeling postmyocardial infarction. Am J Physiol Heart Circ Physiol,2007,293(3):H1900-H1907.
13. Matsumoto R, Yoshiyama M, Omura T, et al. Effects of aldosterone receptor antagonist and angiotensin Ⅱ type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction.Circ J 2004,68(4): 376-382.
14. Willenheimer R. Left ventricular remodeling and dysfunction, Can the process be prevented, Int J Cardiol,2000,72(4):143-150.
15. Peng J, Gurantz D, Tran V, et al. Tumor necrosis factor-alpha induced ATI receptor upregulation enhances angiotensin Ⅱ-mediated cardiac fibroblast responses that favor fibrosis. Circ Res,2002,91(12):1119-1126.
16. Schnee JM, Hsueh WA. Angiotension Ⅱ, adhension, and cardiac fibrosis. Cardiovasc Res,2007,46(2):264-268.
17. Kawano H, Do YS, Kawano Y, et al. Angiotension Ⅱ has multiple profibrotic effects in human cardiac fibroblasts. Circulation,2009,101(10):1130-1137.
18. Frantz S,Adamek A, Wolf J, et al. Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol,2008,103(5):485-492.
19. Van Kats JP, Methot D, Paradis P, et al. Use of a biological peptide pump to study chronic peptide homone action in transgenic mice:direct and indirect effects of angiotensin Ⅱ on the heart. J Biol Chem,2009,276(47):4012-4017.
20. Brower GL, Gardner JD, Forman MF, et al. The relationship between myocardial extracellular matrix remodeling and ventricular function. Eur J Cardiothorac Surg,2006,30(4):604-610.
21. Picard F, Brehm M, Fassbach M, et al. Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP-1) and its inhibitor (TIMP-1) in DCM patients. Clin Res Cardiol,2006,95(5):261-269.
22. Spinale FG. Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function. Physiol Rev,2007,87(4):1285-1342.
23. Chen K, Chen J, Li D, et al. Angiotensin II regulation of collagen type I expression in cardiac fibroblasts:modulation by PPAR-gamma ligand pioglitazone. Hypertension,2004,44(5):655-661.
24. Boengler K, Hilfiker-Kleiner D, Drexler H, et al. The myocardial JAK/STAT pathway:from protection to failure. Pharmacol Therap,2008,120(2):172-185.
25. Chorianopoulos E, Heger T, Lutz M, et al. FGF-inducible 14-kDa protein (fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappa B activation by TWEAK. Basic Res Cardiol,2010,105(2): 301-313.
26. Rouet-Benzineb P, Gontero B. Angiotensin Ⅱ induces nuclear factor-Kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway. J Mol Cell Cardiol,2000,32(10):1767-1778.
27. Webb CS, Bonnema DD. Specific Temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction:relation to left ventricular remodeling.Circulation,2006,114(10):1020-1027.
28. Song G, Hennessy M, Zhao YL, et al. Adrenoceptor blockade alters plasma gelatinase activity in patients with heartfailure and MMP-9 promoter activity in a human cell line (ECV304). Pharmaco Res,2006,54(1):57-64.
29. Duncharme A, Frantz S, Alikawa M, et al. Targeted deletion of matrix metalloproteinase-9 atteunates left ventriclar enlargement and collagen accumulation after experimental myocardial infaction. J Clin Invest,2000,106(1): 55-62.
30. Trueblood NA, Xie Z, Communal C, et al. Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res,2010,88(10):1080-1087.
31. Yutaka Matsui, Nan Jia, Hiroshi Okamoto, et al. Role of osteopentin in cardiac fibrosis and remodeling in angiotensin II induced cardiac hypertrophy. Hypertension, 2009,43(6):1195-1201.
32.梁春,吴宗贵,丁健,等.腱糖蛋白c对大鼠腹腔巨噬细胞活性及其分泌表达基质金属蛋白酶-2,9的影响.中华心血管病杂志,2003,31(5)：365-368.
33. Imanaka-Yoshida K, Hiroe M, Nishikawa T, et al. Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during tissue remodeling after myocardial infarction. Lab Invest,2009,81(7):10-15.
34. Alves TR, da Fonseca AC, Nunes SS, et al. Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells. Exp Cell Res,2011,317(15):2073-2085.
35. Aso N, Tamura A, Nasu M. Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy. Am J Cardiol,2010,94 (11):1468-1650.
36.黄国倩,刘虹,舒先红,等.超声心动图评价粒细胞集落刺激因子动员自身骨髓干细胞对心肌梗死后左心室重构及心功能的影响.中华超声影像学杂志,2004,13(11)：848-852.
37. HusicM, Egstrup K. Usefulness of left ventricular diastolic wall motion abnormality as an early predictor of left ventricular dilation after a first acute myocardial infarction. Am J Cardio,2005,96(9):1186-1189.
38.郭薇,陈斌,王春.实时三维超声心动图对心肌梗死患者左心室重构的评价.中华临床医师杂志,2010,4(6)：752-756.
39. Chung CM, Nakamura S, Tanaka K, et al. Effect of recanalization of chronic total occlusions on global and regional left ventricular function in patients with or without previous myocardial infartion. Catheter Cardiovasc Interv,2003,60(3): 368-374.
40. Niccoli G, Cosentino N, Lombardo A, et al. Angiographic patterns of myocardial reperfusion after primary angioplasty and ventricular remodeling. Coron Artery Dis,2011,22(7):507-514.
41. Miura T, Yuda S. Are treatment effects of ACEI and ARB in post-MI patients homogeneous? Circ J,2009,73(5):820-821.
42.王振涛,王硕仁,李敏,等.活血益气注射液治疗心衰大鼠心气虚证的研究.中药药理与临床,2000,16(增刊)：73-75.
43.董国菊,刘剑刚,史大卓,等.愈心梗液对急性心肌梗死大鼠心肌能量代谢和内皮功能障碍的影响.中国中医急症,2005,14(9)：872-874.
1. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part 1. Circulation,2003, 108(14):1664-1672.
2. Kolodgie FD, Virmani R, Burke AP, et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004,90(12):1385-1391.
3. 刘华,王永武.冠心病血运重建治疗进展.同济大学学报(医学版),2003,24(4)：330-333.
4. 中华医学会心血管病学分会.不稳定性心绞痛和非ST段抬高心肌梗死诊断与治疗指南.中华心血管病杂志,2007,35(4)：295-304.
5. Armstrong, EricR Bates, Lee A Green, et al.2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. JACC,2008,51(2):210-247.
6. Tanaka A, Kawarabayashi T, Nishibori Y, et al. No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 2002, 105(18):2148-2152.
7. Resnic FS, Wainstein MW, Lee MK, et al. No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J,2003,145(1):42-46.
8. HuangY, Salu k, WangL, et al. Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine cornary model. J Invasive Cardiol,2005,17(8): 142-148.
9. Mauri L, Hsich WH, Massaro JM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med,2007,356(5):1020-1029.
10. Kentaro Ejiri, Masaharu Ishihara, Kazuoki Dai, et al. Three-Year Follow-up of Sirolimus-Eluting Stents vs. Bare Metal Stents for Acute Myocardial Infarction. Circ,2012,76(1):65-70
11. Hee-Hwa Ho, Vincent Pong; Chung-Wah Siu, et al. Long-term Clinical Outcomes of Drug-Eluting Stents vs. Bare-Metal Stents in Chinese Patients. Clin. Cardiol, 2010,33(6):E22-E29.
12. Victor M.G, Legrand Patrick, W. Serruys, et al. Three-Year Outcome After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease. Circulation,2004,109(5):1114-1120.
13. Lisette Okkels Jensen, Michael Maeng, Per Thayssen, et al. Clinical Outcome After Primary Percutaneous Coronary Intervention With Drug-Eluting and Bare Metal Stents in Patients With ST-Segment Elevation Myocardial Infarction. Circ Cardiovasc Interv,2008,1(2):176-184.
14.中医研究院西苑医院内科,东直门医院内科,广安门医院内科,北京宣武医院内科.以“抗心梗合剂”为主治疗急性心肌梗塞118例疗效分析.中华内科杂志,1976,12(4)：212-215.
15.徐浩,史大卓,陈可冀.芎芍胶囊预防冠状动脉介入治疗后再狭窄的临床研究.中国中西医结合杂志,2000,20(7)：494-497.
16.李永强,金枚,仇盛蕾,等.益气养阴活血中药对急性心肌梗死患者血运重建后心室壁运动的影响.中国中西医结合杂志,2009,29(4)：300-304.
17.王承龙,殷惠军,史大卓,等.西洋参茎叶皂苷心血管药理研究概述.中药新药与临床药理,2006,17(1)：76-78.
18.刘雪东,李伟东,蔡宝昌,等.当归化学成分及对心脑血管系统作用研究进展.南京中医药大学学报,2010,26(2)：155-157.
19.李善春,杨军,方毅民,等.川芎嗪对急性心梗死急诊冠状动脉介入治疗后“心肌无复流”的影响.中华核医学杂志,2006,26(6)：366-369.
20. J. J. Thune, J. Signorovitch, L. Kober, et al. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-riskmyocardial infarction. Hypertension 2008,51(1):48-54.
21. Rakugi H, Yu H, A. Kamitani, et al. Links between hypertension and myocardial infarction. American Heart Journal,1996,132(1):213-221.
22. D. G. Kang, M. H. Jeong, Y. Ahn, et al. Clinical effects of hypertension on the mortality of patients with acute myocardial infarction. Journal of Korean Medical Science,2009,24(5):800-806.,
23. He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet,2009,374 (97):1765-1772.
24. Schillaci G, Mannarino MR, Pucci G, et al. Age-specific relationship of aortic pulse wave velocity with left ventricular geometry and function in hypertension. Hypertension,2007,49(2):317-21.
25. Chirinos JA, Zanlbrlo JP, Chakko S, et al. Aortic Pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Circulation,2005,45(4):980-985.
26. Nissen SE, Tuzeu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure; The CAMELOT study:A randomized controlled trial. JAMA,2004,292(18): 2217-2225.
27. Madhavan S, Ooi WL, Cohen H, et al. Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction. Hypertension,1994, 23(3):395-401.
28. Pedersen SS, Versteeg H, Denollet J, et al. Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting. Qual Life Res.,2011,20(4):559-567.
29.邓艳红,董吁钢,陈丹丹,等.堪萨斯城生存质量表对慢性心力衰竭患者生存质量评估的可行性评价.中华心血管病杂志,2004,32(8)：676-679.
30. Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med.,2008,359(7):677-687.
31. Packard CJ, Ford I, Robertson M, et al. Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation,2005,112(20): 3058-3065.
32. Ichiro Matsumoto, Yuichi Miyake, Mizuki Mizukawa, et al. Impact of Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio on Long-Term Outcome in Patients Undergoing Percutaneous Coronary Intervention. Circulation Journal,2011,75(2):905-910.
33. Walldius G, Jungner I, Aastveit AH, et al. The apoB/apoAl ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med, 2004,42(12):1355-1363.
34. Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. Am Coll Cardiol,2008,51(7):724-730.
35.顾复生.对大型他汀类药物临床研究强化降脂治疗的分析.中华老年医学杂志,2008,27(8)：636-638.
36.邹凤军,丁五麟,张小杭,等.超声心动图评价急性心肌梗死后左室扩大对左室收缩功能的影响.北京医学,2005,27(6)：347-370.
37. Cohen M, Charney R, Hershma R, et al. Reversal of chronic ischemic myocardial dysfunction after transluminal coronary angioplasty. J Am Cardiol,1988,12: 1193-1198.
38.蒋利,沈卫峰,张建盛,等.多支血管病变患者冠状动脉内支架术疗效观察临床心血管病杂志,2002,18(10)：481-483.
39. Serruys PW, Unger F, Sousa JE, et al. Comparison of coronary artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med,2001, 344:1117-1124.
40.杨跃进,罗彤,高润霖,等.首次心肌梗死后择期经皮冠状动脉介入治疗的长期预后分析.中华心血管病杂志,2003,31(11)：818-821.
41. RodriguezA, Benrardi V, Navia J, et al. Argentine randomized study:Coronary angioplasty with stenting versus coronary bypass surgery in patients with multiplevessel disease (ERACI Ⅱ):30-day an done-year fllow-up results. J Am Coll Cardiol,2001,37:51-58.
1. Gregory M, Fomovsky, Stavros Thomopoulos, et al. Contribution of Extracellular Matrix to the Mechanical Propertiesof the Heart. J Mol Cell Cardiol.2009,29(3): 490-496.
2. Rogelio Zamilpa, Merry L. Lindsey. Extracellular matrix turnover and signaling during cardiac remodeling following MI:causes and consequences. J Mol Cell Cardiol.2010,48(3):558-563.
3.张松飞,王晓娜,潘涛,等.中医药对心肌缺血再灌注损伤的保护作用及机制的实验研究进展.中国中医急症,2011,20(3)：432-435.
4. Janicki J.S, Brower G.L, The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Fail.2002,8 (6 Suppl):319-325.
5.吴爱明,赵明镜,张冬梅,等.心梗后心力衰竭模型大鼠中医证候特点及心脏的超声评价.中国中西医结合杂志,2007,27(3)：227-229.
6. M.G. Sutton, N. Shaipe. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000,101(25):2981-2988.
7. Norman Sharpe. Cardiac Remodeling in Coronary Artery Disease. Am J Cardiol 2004; 93(suppl):17-20.
8. 郭薇,陈斌,王春,等.实时三维超声心动图评估心肌梗死患者的左室变化.中国超声医学杂志,2009,25(3)：281-284.
9. Litwin SE, Katz SE, Morgan JP, et al. Serial echocardiographic assessment of left ventdcular geometry and function alter large myocardial infarction in the rat. Circulation 1994,89(1):345-354.
10. Prunier F, Gaertner R, Louedec L, et al. Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats. Am J Physiol Heart Circ Physiol,2002,283(1):346-352.
11. Kazmi KA, Iqbal SP, Bakr A, et al. Admission creatine kinase as a prognostic marker in acute myocardial infarction. J Pak Med Assoc 2009,59(12):819-822.
12. Vuolteenaho O, Alakopsala M, Ruskoaho H. BNP as a biomarker in heart disease. Adv Clin Chem,2005,40 (1):1-36.
13. Eugene Braunwald. Biomarkers in Heart Failure. N Engl J Med 2008,358(20): 2148-2159.
14. Alans S, Peter A. Cardiac natfiuretic peptides:A proteomic window to cardiac function and clinical management. Rev Cardiovasc Med,2009,4(14):3-12.
15.吴学明,左志通,陈艳红,等.血浆脑利钠肽浓度与心室重构的关系.中国微循环,2007,11(3)：195-197.
1. Hutchinson Kirk R, Stewart JA Jr, Lucchesi P, et al. Extracellular matrix remodeling during the progression of volume overload-induced heart failure. Journal of Molecular and Cellular Cardiology,2010,48(3):564-569.
2. Borg TK, Baudino TA. Dynamic interactions between the cellular components of the heart and the extracellular matrix. Pflugers Arch,2011,462(1):69-74.
3. Holmes JW, Borg TK, Covell JW. Structure and mechanics of healing myocardial infarcts. Annu Rev Biomed Eng,2005,7:223-253.
4. Murtuza B, Suzuki K, Bou Gharios G, et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA,2004,101(12):4216-4221.
5. Matsumura S, Iwanaga S, Mochizuki S, et al. Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice. J Clin Invest,2005,115(3):599-609.
6. Li J, Schwimmbeck PL, Tschope C, et al. Collagen degradation in a murine myocarditis model:relevance of matrix metalloproteinase in association with inflammatory induction. Cardiovasc Res,2002,56(2):235-247.
7. Bradham WS, Bozkurt B, Gunasinghe H, et al. Tumor necrosis factor aand myocardial remodeling in progression of heart failure:a current perspective. Cardiovasc Res,2002,53(4):822-830.
8. Nakano M, Knowlton AA, Dibbs Z, et al. Tumor necrosis factor-alpha confers resistance to hypoxic injury in the adult mammalian cardiac myocyte. Circulation, 2004,97(14):1392-1400.
9. Kubota T, McTieman CF, Frye CS, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific over expression of tumor necrosis factor-alpha. Cire Res, 2007,81(4):627-635.
10.王鹏飞,刘振,刘玲玲,等.白细胞介素1p和基质蛋白酶2、基质蛋白酶9/基质蛋白抑制因子1在左室重构中的动态表达及内在联系.临床医学,2010,30(3)：96-99.
11. Johannes Lagethon Bjornstad, Ivar Sjaastad, et al. Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload. European Heart Journal,2011,32(2):236-245.
12. Deten A, Holzl A, Leicht M, et al. Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats. J Mol Cell Cardiol,2006,33(6):1191-1207.
13.赵永锋,朱文晖,唐水娟,等.心梗后大鼠应变、应变率成像及心室重塑研究.中国超声医学杂志,2011,27(4)：293-296.
14. Herpel E, Pritsch M, Koch A, et al. Interstitial fibrosis in the heart:differences in extracellular matrix proteins and matrix metalloproteinases in end-stage dilated, ischemic and valvular cardiomyopathy. Histopathology,2006,48(6):736-747.
15. Espira L, Michael PC. Emerging concepts in cardiac matrix biology. Canadian journal of physiology and pharmacology,2009,87(12):996-1008.
16. Suzuki N, Yokoyama F, Nomizu M. Functional sites in the laminin alpha chains. Connect Tissue Res,2005,46(3):142-152.
17. Sarah McCurdy, Catalin F. Baicu, Stephane Heymans, et al. Cardiac Extracellular Matrix Remodeling:Fibrillar Collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC). J Mol Cell Cardiol,2010,48(3):544-549.
18.宋颖,王丽萍,胡霞,等.急性心肌梗死后血清Ⅲ型前胶原蛋白与左室功能变化关系的临床研究.中国急救医学,2003,23(4)：274-275.
19. Moshal KS, Tyagi N, Moss V, et al. Early induction of matrix metalloproteinase-9 transducers signalling in human heart end stage failure. J Cell Mol Med,2005,9(3): 704-713.
20. Ducharme A, Frantz S, Aikawa M, et al.Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest,2000,106(7): 55-62.
21. Kalela A, Koivu TA, Sisto T, et al. Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease. Seand J Clin Lab Invest,2002, 62(5):337-342.
22. Raaf L, Noll C, Cherifi Mel H, et al. Myocardial fibrosis and TGFB expression in hyperhomocysteinemic rats. Mol Cell Biochem,2011,347(12):63-70.
23. Moore L, Fan D, Basu R, et al. Tissue inhibitor of metalloproteinases (TIMPs) in heart failure. Heart Fail Rev,2011,65(2):72-76.
24. Nagase H, Visse R, Murphy G. Structure and function of matrix metal proteinases and TIMPs. Circ Res,2006,69(3):562-573.
25. Espira L, Michael PC. Emerging concepts in cardiac matrix biology. Canadian journal of physiology and pharmacology,2009,87(12):996-1008.
26. Mahipal Singh, Cerrone R. Foster, Suman Dalal, et al. Osteopontin:role in extracellular matrix deposition and myocardial remodeling post-MI. J Mol Cell Cardiol.,2010,48(3):538-543.
27. Kruzynska-Frejtag A, MachnickiM, Rogers R, et al. Osteopontin (an osteoblast-specific factor) is expressed within the embryonic mouse heart during valve formation. Mech Dev,2004,103(2):183-188.
28.张玉玲,周淑娴,雷娟,等.血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白表达及胶原沉积的影响.中国循环杂志,2007,22(4)：307-310.
29. Kupfahl C, Pink D, Friedrich K, et al. Angiotensin Ⅱ directly increases transforming growth factor b1 and osteopontin and indirectly affects collagen mRNA expression in the human heart. Cardiovasc Res.,2000,46(4):463-475.
30. Brellier F, Tucker RP, Chiquet-Ehrismann R. Tenascins and-their implications in diseases and tissue mechanics. Scand J Med Sci Sports,2009,19(4):511-519.
31. Chiquet-Ehrismann R, Chiquet M. Tenascins:regulation and putative functions during pathological stress. J Pathol 2003,200(9):488-499.
32.赵学,钟才进,吴宗贵,等.骨桥蛋白通过促血管新生调节心肌梗死后左室重构.上海医学,2005,43(5)：301-303.
33. Fujimoto N, Onishi K, Sato A, et al. Incremental prognostic values of serum tenascin-C levels with blood B-type natriuretic peptide testing at discharge in patients with dilated cardiomyopathy and decompensated heart failure. J Card Fail., 2009,15(10):898-905.
34. Jian B, Jones PL, Li Q, et al. Matrix metalloproteinase 9 is associated with tenascin-C in calcilic aortic stenosis. Am J Path,2001,159(1):321-327.
35. Terasaki F, Okamoto H, Onishi K, et al. Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy. Circ J 2007,71(5):327-330.
36. Basso N, Cini R, Pietrelli A, et al. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol,2007,293(7):1351-1358.
37. Ikeuchi M, Tsutsui H, Shiomi T, et al. Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction. Cardiovasc Res,2004,64(6):526-535.
38. Marcin Bujak, Nikolaos G, Frangogiannis. The role of TGF-β1 Signaling in myocardial Infarction and Cardiac Remodeling. Cardiovasc Res.,2007,74(2): 184-195.
39. Teekakirikul P, Eminnga S, Toka O, et al. Cardiac fibrosis in mice with hypenrophic cardiomyopathy is mediated by nonmyocyte proliferation and requires TGF-β1 J Clin Invest,2010,120(10):3520-3529.
40. Lindholm L H. Valsartan treatment of hypertension-does value add value? Lancet, 2004,363(4):2010-2011.
41.杜广胜,邱强,马业新,等.缬沙坦对心肌缺血坏死后心肌转化生长因子-β及Ⅰ、Ⅲ型胶原表达的影响.中国急救医学,2005,25(5)：344-345.
42.王承龙,殷惠军,史大卓,等.西洋参茎叶皂苷心血管药理研究概述.中药新药与临床药理,2006,17(1)：76-78.
43.范宝晶,裴非,赵学忠,等.西洋参茎叶总皂苷对心肌肥厚大鼠血管内皮功能的影响.中国老年学杂志,2009,29(7)：811-812.
44.王承龙,史大卓,殷惠军,等.西洋参茎叶总皂苷对急性心肌梗死大鼠心肌VEGF、bFGF表达及血管新生的影响.中国中西医结合杂志,2007,27(4)：331-334.
45.刘芬,王秋静,吕文伟,等.赤芍总甙对犬急性缺血心肌的保护作用.中国临床康复,2005,9(31)：136-138.
46.孙大军,祁功才,吕文伟,等.赤芍总苷对实验性血栓形成的影响及其作用机制.中国老年学杂志,2006,26(8)：1080-1081.
47.朱慧民,祝彼得.赤芍防止高脂喂养兔颈总动脉球囊损伤术后血管狭窄的实验研究.中国中西医结合杂志,2004,24(6)：538-540.
48. Elena MV de Cavanagh, Marcelo Ferder, Felipe Inserra, et al. Angiotensin II, mitochondria, cytoskeletal and extracellular matrix connections:an integrating viewpoint. Am J Physiol Heart Circ Physiol,2009,296(3):H550-H558.