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目的:通过通心络胶囊对载脂蛋白E基因敲除小鼠[ApoE(-/-)]冠状动脉斑块和心肌病理组织学及其胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、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,探究其治疗冠状动脉脉粥样硬化(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,随机分为模型组和辛伐他汀组等4组,后者分别给予辛伐他汀及高、中、低剂量的通心络胶囊进行干预56d;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血脂、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,通心络胶囊低、中、高各剂量组均分分别为4.5±1.71、3.12±1.81、2.38±2.34;与模型组比较,通心络胶囊低剂量组P<0.05,中、高剂量组和辛伐他汀组均为P<0.01;通心络胶囊中、高剂量组与辛伐他汀组比较P>0.05。模型组血清TC、TG和LDL-C均明显增高,HDL-C下降,与正常组相比P<0.05;通心络胶囊中、高剂量组TC、TG和LDL-C均明显低于、HDL-C水平高于模型组P<0.05或P<0.01,与辛伐他汀组相比P>0.05。模型组第28天开始,血中CEC显著增多,与正常组相比P<0.01,与通心络胶囊高剂量组在造模后第28、56、84天相比P<0.05或P<0.01,与中剂量组在造模后第28、84天相比P<0.05。与模型组小鼠血清ET含量相比,高于正常组P<0.05,与通心络胶囊三个剂量组相比P<0.01。通心络胶囊高剂量组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,中剂量组MMP-9水平低于模型组P<0.05。结论:通心络胶囊具有降低血脂、抗冠状动脉粥样硬化和稳定斑块的作用,其机制可能与调脂、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 effect of Tongxinluo capsule on coronary artery plaque and myocardial histopathology, cholesterol (TC) and low density lipoprotein (LDL-C) in apolipoprotein E knockout mice [ApoE , Triglyceride (TG), high density lipoprotein (HDL-C), circulating endothelial cells (CEC), endothelin (ET), matrix metalloproteinase-1 (MMP- 9), tissue inhibitor of metalloproteinase 1 (TIMP1) and other indicators of intervention to explore the treatment of coronary atherosclerosis (AS) of the therapeutic mechanism. Methods: Forty ApoE (- / -) mice were used as the experimental group. Coronary AS model was established and randomly divided into 4 groups: model group and simvastatin group. Simvastatin and high, Tongxinluo Capsule for 56 days. Eight mice with the same line were selected as normal control group. The changes of histopathology, blood lipid, CEC, ET, MMP-1, MMP-9 and TIMP1 in coronary artery plaque and myocardium in each group were observed. Results: The lesions of coronary artery in model group were mainly located in the small branches, myocardial cells and myocardial interstitium in the myocardium, which were all divided into 6.33 ± 1.48, 2.62 ± 2.25 in simvastatin group, High dose of each group were 4.5 ± 1.71,3.12 ± 1.81,2.38 ± 2.34; Compared with the model group, Tongxinluo capsule low dose group P <0.05, medium and high dose group and simvastatin group were P < 0.01; Tongxinluo capsule, high-dose group and simvastatin group P> 0.05. TC, TG and LDL-C in model group were significantly higher, HDL-C decreased, P <0.05 compared with normal group; TC, TG and LDL-C in Tongxinluo capsule were significantly lower than those in HDL The level of C was higher than that of model group (P <0.05 or P <0.01), P> 0.05 compared with simvastatin group. Compared with the normal group, P <0.01, P <0.05 or P <0.01 compared with the high dose group of Tongxinluo capsule on the 28th, 56th and 84th days after model establishment , P <0.05 compared with the 28th and 84th day after the model group was established. Compared with the model group, the content of serum ET in the model group was significantly higher than that in the normal group (P <0.05), P <0.01 compared with the three dose groups of Tongxinluo capsule. The levels of MMP-1 and MMP-9 in Tongxinluo Capsule high-dose group were lower than those in model group, and the levels of TIMP1 in model group were higher than those in model group (P <0.05 or P <0.01). CONCLUSION: Tongxinluo capsule can reduce blood lipid, anti-coronary atherosclerosis and stable plaque. Its mechanism may be related to lipid regulation, improving endothelial cell dysfunction (EDF) and inhibiting vascular remodeling.