气血并治方有效组分对载脂蛋白E基因敲除小鼠动脉粥样硬化不稳定斑块的干预作用  

Effects of components of water extract from Qixue Bingzhi Fang on atherosclerotic unstable plaque of apolipoprotein E deficient mice

作　　者：刘剑刚[1] 董国菊[1] 史大卓[1] 王永炎[2] 

机构地区：[1]中国中医科学院西苑医院心血管科,北京100091 [2]中国中医科学院,北京100700

出　　处：《中国药理学与毒理学杂志》2008年第4期263-269,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金项目(30200370);国家重点基础研究发展规划项目(G1999054405)~~

摘　　要：目的探讨气血并治方水提取物有效组分(CWQB)配伍对载脂蛋E基因敲除(ApoE-)小鼠晚期动脉粥样硬化不稳定斑块的干预作用及其可能的作用机制。方法6周龄ApoE-小鼠,给予高脂饲料,随机分为模型组、辛伐他汀2.5mg·kg-1组、CWQB 72和360mg·kg-1组。从24周龄起灌胃给药,每日1次,连续12周。同时取同龄C57BL/6小鼠作为正常对照。36周龄时麻醉处死,检测血脂水平和主动脉病理变化,免疫组织化学及计算机图像处理系统分析主动脉斑块中巨噬细胞内CD68的表达和平滑肌细胞内α-肌动蛋白的表达。结果CWQB及辛伐他汀均能降低小鼠的血脂水平,降低其胆固醇含量,升高高密度脂蛋白水平。CWQB大剂量组和辛伐他汀组可见主动脉斑块纤维帽厚度增加,斑块面积和管腔面积的比值下降;斑块中平滑肌细胞内α-肌动蛋白表达增加,巨噬细胞内CD68表达减少。结论CWQB具有一定的消减和稳定主动脉斑块的作用,其机制可能与其降低血脂水平、减少斑块内巨噬细胞浸润和增加血管平滑肌细胞数量有关。AIM To investigate whether components of water extract from Qixue Bingzhi Fang （CWQB） have effects on unstable plaque of atherosclerosis in apolipoprotein E deficient （ApoE^-） mice and the possible mechanisms. METHODS ApoE^ - mice （ 6 weeks old ） , given high fat diet, randomly divided into model, simvastatin 2.5 mg·kg^-1, CWQB 72 and 360 mg·kg^-1 groups, 10 mice in each group. From 24 weeks old, the mice were given ig tap water, simvastatin or CWQB, once daily for 12 weeks. The normal C57BL/6 mice with the same age as ApoE^ - mice were taken as normal control, and received normal diet. Rats were sacrificed at 36 weeks. Then blood lipids were detected, aorta pathological changes were observed, and expressions of CD68 in macrophages of plaque and α-actin in vascular smooth muscle cells （VSMC） of aorta were determined with immuohistochemistry and computer image processing system. RESULTS Low and high doses of CWQB and simvastatin decreased the contents of blood lipids and increased the levelof high density lipoprotein. The fibrous thickness of plaque significantly increased plaque area/vascular size decreased in dose of CWQB and high dose of CWQB simvastatin groups. cap and high Both and simvastatin reduced CD68 expression in macrophages of plaque and increased expression of α-actin in VSMC. CONCLUSION CWQB have some beneficial effects on decreasing and stabilizing atherosclerotic plaque in aorta, which may be related to adjusting blood lipid, decreasing macrophage infiltration and increasing VSMC in atherosclerotic plaque of aorta.

关 键 词：气血并治方 载脂蛋白E类 小鼠 基因敲除 动脉硬化 巨噬细胞 肌 平滑 血管 

分 类 号：R285.5[医药卫生—中药学] R363[医药卫生—中医学]