气血并治方组分配伍防治载脂蛋白E基因敲除小鼠早期动脉粥样硬化的实验研究  

Effects of water extractives of a qi and blood regulating prescription on early atherosclerosis of apolipoprotein E-deficient mice

作　　者：董国菊[1] 刘剑刚[1] 史大卓[1] 王永炎[2] 栾连军[3] 程翼宇[3] 

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,北京100091 [3]浙江大学药学院中药科学与工程学系,浙江杭州310027

出　　处：《中西医结合学报》2007年第1期45-49,共5页Journal of Chinese Integrative Medicine

基　　金：国家重点基础研究发展规划资助项目(No.G1999054405)

摘　　要：目的:观察气血并治方水提取物组分配伍(以下简称气血并治方)防治载脂蛋白E基因敲除(apolipoproteinE-deficient,ApoE-)小鼠早期(19周龄)动脉粥样硬化不稳定斑块形成的作用。方法:40只6周龄的ApoE-小鼠,给予高脂饮食。随机分为4组:气血并治方高剂量治疗组(360mg/kg)、气血并治方低剂量治疗组(72mg/kg)、辛伐他汀治疗组(25mg/kg)和模型组,每组10只。同时取同龄的具有相同遗传背景的C57BL/6小鼠10只作为空白对照组。从15周龄至19周龄连续给药,气血并治方高剂量治疗组、气血并治方低剂量治疗组和辛伐他汀治疗组均给予相应药物灌胃。模型组和空白对照组给予等量自来水。19周时麻醉处死,检测动物血脂水平,免疫组织化学和计算机图像系统分析斑块构成、斑块积分、斑块内巨噬细胞和血管平滑肌细胞的含量。结果:与模型组比较,气血并治方高剂量治疗组能明显降低小鼠的低密度脂蛋白胆固醇水平,辛伐他汀能明显降低小鼠的总胆固醇和低密度脂蛋白胆固醇水平(P<0.01),而气血并治方高剂量治疗组和辛伐他汀治疗组均能明显增加小鼠斑块的纤维帽厚度和小鼠斑块内血管平滑肌细胞的数量(P<0.05),减少斑块内巨噬细胞的数量和脂质中心面积与斑块面积之比(P<0.01)。结论:气血并治方和辛伐他汀均可以干预ApoE-小鼠早期动脉粥样硬化的形成,并能降低动物的血脂水平,在一定程度上有消减斑块、改变斑块构成和稳定斑块的作用。Objective： To investigate whether the water extractives of regulating qi and blood prescription （WQBP） had effects on early atherosclerosis of apolipoprotein E-deficient mice （ApoE-mice） at the age of 19 weeks or not, and to explore the possible mechanisms. Methods： Forty ApoE mice, six weeks of age, were given high-fat diet and randomly divided into four groups： high-dose WQBP-treated group （360 mg/kg）, low-dose WQBP-treated group （72 mg/kg）, simvastatin-treated group （25 mg/kg） and untreated group, with ten mice in each group. Meanwhile, ten C57BL/6 mice of same genetic background were allocated to normal control group. Mice in the high- and low- dose WQBP-treated groups and simvastatin-treated group were administered with corresponding drugs from the 15 to 19 weeks. Mice in the untreated and normal control groups were administered with isovolumic water. Sacrificed at 19 weeks, the level of blood-lipid, the plaque construction, plaque integral, and the contents of plaque macrophages and vessel smooth muscle cells of the mice were analyzed by immunohistochemical method and a computer picture processing system. Results： Compared to the untreated group, high-dose WQBP group could obviously decrease the level of lowdensity lipoprotein cholesterol （LDL-C）. Simvastatin group could decrease the levels of LDL-C and total cholesterol （TC） （P〈0.01）. In high-dose WQBP-treatedgroupand simvastatin-treatedgroup, the thickness of fiber cap and the quantities of vessel smooth muscle cells increased （P〈0.05）, the quantities of plaque macrophages and the ratio of lipid and plaque reduced （P〈0.01）. Conclusion： WQBP and simvastatin can interfere in early atherosclerosis of ApoE mice, attenuate and stabilize plaque in some extent. The mechanisms may include adjusting blood lipid, decreasing macrophage number and increasing the quantities of vessel smooth muscle cells.

关 键 词：基因敲除小鼠 动脉粥样硬化 低密度脂蛋白胆固醇 总胆固醇 

分 类 号：R285[医药卫生—中药学]