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目的通过通心络胶囊(以下简称“通心络”)对载脂蛋白E基因敲除小鼠[ApoE(-/-)]冠状动脉斑块和心肌病理组织学及其循环内皮细胞(CEC)、内皮素(ET)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂1(TIMP1)等指标的干预变化,探究其治疗冠心病(CHD)动脉粥样硬化(AS)的疗效机制。方法将40只ApoE(-/-)小鼠作为实验组,建立冠状AS模型,随机分为模型组、辛伐他汀组和通心络高、中、低剂量组,分别给予相应药物干预8周;另选8只同系的小鼠作为正常对照组。观察各组小鼠冠状动脉斑块和心肌病理组织学及其CEC、ET、MMP-1、MMP-9、TIMP1等指标的变化。结果模型组小鼠冠状动脉病变主要位于心肌内的小分支、心肌细胞、心肌间质,均分为6.33±1.48。辛伐他汀组均分为2.62±2.25;通心络低、中、高剂量组均分为4.5±1.71、3.12±1.81、2.38±2.34。各给药组与模型组比较,P<0.05或P<0.01;通心络中、高剂量组与辛伐他汀组比较,P>0.05。模型组第4周开始,血中CEC显著增多,与正常组相比,P<0.01,与通心络高剂量组在造模后第4、8、12周相比,P<0.05或P<0.01,与中剂量组在造模后第4、12周相比,P<0.05。模型组小鼠血清ET含量高于正常组,P<0.05,与通心络3个剂量组相比,P<0.01。通心络高剂量组MMP-1和MMP-9水平均低于模型组,而TIMP1水平高于模型组,P<0.05或P<0.01,通心络中剂量组MMP-9水平低于模型组,P<0.05。结论通心络具有抗冠状AS和稳定斑块的作用,其机制可能与改善血管内皮细胞功能障碍(EDF)和抑制血管重构相关。
Objective To investigate the effects of Tongxinluo capsule on coronary plaque and cardiac histopathology of apolipoprotein E knockout mice [ApoE (- / -)] and its circulating endothelial cells (CEC), endothelin (ET), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP1) Efficacy of coronary heart disease (CHD) on atherosclerosis (AS). Methods Forty ApoE (- / -) mice were used as experimental group. Coronary AS model was established and randomly divided into model group, simvastatin group and Tongxinluo high, medium and low dose groups. The rats were given the corresponding drug for 8 weeks Eight mice with the same line were selected as normal control group. The changes of coronary artery plaque and myocardial histopathology, CEC, ET, MMP-1, MMP-9 and TIMP1 were observed in each group. Results The coronary lesions in the model group were mainly located in the small branches, myocardial cells and myocardial interstitium in the myocardium, all of which were divided into 6.33 ± 1.48. Simvastatin group were divided into 2.62 ± 2.25; Tongxinluo low, medium and high dose group were divided into 4.5 ± 1.71,3.12 ± 1.81,2.38 ± 2.34. P <0.05 or P <0.01 in each treatment group compared with model group; P> 0.05 in Tongxinluo middle and high dose group and simvastatin group. Compared with the normal group, the CEC in the model group increased significantly at the 4th week, P <0.01, compared with the high dose group of Tongxinluo 4, 8, and 12 weeks after modeling (P <0.05 or P < 0.01, P <0.05 compared with the 4th and 12th week after the model group. The content of serum ET in model group was higher than that in normal group, P <0.05, P <0.01 compared with the three dose groups of Tongxinluo. Tongxinluo high-dose group MMP-1 and MMP-9 levels were lower than the model group, and TIMP1 levels higher than the model group, P <0.05 or P <0.01, Tongxinluo MMP-9 levels were lower than the model group , P <0.05. Conclusion Tongxinluo has anti-coronary AS and stable plaque, the mechanism may be related to the improvement of vascular endothelial dysfunction (EDF) and inhibition of vascular remodeling.