通心络胶囊对载脂蛋白E基因敲除小鼠冠状动脉粥样硬化的影响及其机理研究  

Influence of Tongxinluo Capsule on Coronary Atherosclerosis of Apolipoprotein E Gene Knockout Mice and Its Mechanism

作　　者：韩旭[1] 李七一[1] 夏卫军[1] 赖仁胜[1] 陈小虎[1] 郭宏敏[1] 赵惠[1] 刘福明[1] 朱波[1] 

机构地区：[1]江苏省中医院心血管内科,江苏南京210029

出　　处：《中国中医药信息杂志》2011年第2期37-40,共4页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：江苏省自然科学基金(BK2006157)

摘　　要：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 explore the therapeutic mechanism of Tongxinluo capsule in treating atherosclerosis （AS） of coronary heart disease by measuring the changes of coronary plaques, myocardial histopathology and circulating endothelial cell （CEC）, endothelin （ET）, matrix metalloproteinase-1 （MMP-1）, matrix metalloproteinase-9 （MMP-9）, tissue inhibitors of matrix metalloproteinasel （TIMP1） of Apolipoprotein E gene knockout mice [ApoE（-/-）] intervened by Tongxinluo capsule. Methods Forty Apolipoprotein E gene knockout mice [ApoE（-/-）] were taken as the experimental group to establish the models of coronary atherosclerosis, and randomly divided into 5 groups （model group, Simvastatin group and high, middle, low dose of Tongxinluo group）. The treatment groups were intervened for 8 weeks by Tongxinluo capsule of their respective doses and Simvastain capsules correspondingly, with other 8 isogeneic mice as the normal control group. The changes of coronary plaques, myocardial histopathology and CEC, ET, MMP-1, MMP-9, TIMP1 in each group were observed. Results The lesion of coronary in mice of the model group were mostly located at small branches in cardiac muscle, cardiac muscle, cell, myocardial interstitium, and the average score was 6.33 ± 1.48, which of Simvastatin group was 2.62±2.25, and the low, middle, high doses of Tongxinluo capsule was 4.5± 1.71, 3.12 ± 1.81, 2.38±2.34 respectively. Compared with the model group, all treatment groups had significant difference （P〈0.05 or P 〈0.01）. There were no statistically significant differences between Simvastatin group and high and middle dose of Tongxinluo group （P〈0.05）. Blood CEC of the model group increased considerably compared with the normal group （P〈0.01） from the fourth week, the high dose of Tongxinluo capsule （P〈0.05 or P〈0.01） at the fourth, eighth, twelfth week and the middle dose of Tongxinluo capsule （P〈0.05） at the fourth, twelfth week. Blood ET of model group was higher compared with the

关 键 词：通心络胶囊 载脂蛋白E基因敲除小鼠 冠状动脉粥样硬化 病理组织学 循环内皮细胞 内皮素 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 

分 类 号：R285.5[医药卫生—中药学]