刺芒柄花素调节血脂代谢及改善动脉粥样硬化病变的实验研究  

Effect of formononetin on abnormal lipid metabolism and atherosclerosis

作　　者：赵培[1] 杨媛[1] 徐扬[1] 李雪[1] 张晶[1] 姜威[1] 洪斌[1] 司书毅[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2009年第10期925-929,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金项目(30472026);国家中央级公益性科研院所基本科研业务专项(IMBF-20060201)

摘　　要：目的:研究刺芒柄花素上调SR-BI蛋白表达和影响血脂代谢、肝脏脂肪化及动脉粥样硬化病变作用。方法:利用高通量筛选模型评价刺芒柄花素对CLA-1/hSR-BI蛋白基因的转录激活效用。通过高脂饲料喂养金黄地鼠21d,建立实验性高脂血症动物模型。给予不同剂量的刺芒柄花素,28d后测定血浆总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白-胆固醇(LDL-C)及高密度脂蛋白-胆固醇(HDL-C)含量。组织切片HE染色观察肝脏病变,胸主动脉硬化情况。结果:刺芒柄花素可以在一定程度上降低高脂血症金黄地鼠血清TC,TG和LDL-C,升高HDL-C;改善肝脂肪化、减轻炎性细胞浸润;抑制胸主动脉壁内膜下泡沫细胞形成和中膜平滑肌增生。结论:刺芒柄花素具有调节体内血脂代谢,抑制肝脏脂肪沉积和预防动脉粥样硬化效果。Objective： Formononetin was found to be an up-regulator of SR-BI expression by a cell-based high throughput screening. Here we examined whether formononetin affects blood lipid metabolism, atherosclerosis and hepatic lipogenesis in hypercholesterolemic hamsters. Methods： Firstly, formononetin was further evaluated for its up-regulating activity of SR-BI expression in a cell-based high throughput screening model. Then, hypercholesterolemia in golden hamsters was induced by feeding a high-fat diet for 21 days, and the hamsters were administrated with different doses of formononetin. The levels of TC, TG, LDL-C, and HDL-C in serum were analyzed. Finally, pathological changes of liver li mononetin obviously reduced the leve po ls genesis and atherosclerosis in aorta thoracalis were examined. Results： Formononetin obviously reduced the levels of TC （ P 〈 0.05 ）, TG （ P 〈 0.01 ） and LDL-C （ P 〈 0.01 ）, and increased the levels of HDL（P 〈 0.05 ） as compared with control hypercholesterolemic hamsters. Pathological examination showed that formononetin attenuated hepatic cell steatosis and inflammatory cell recruiting; it also reduced accumulation of foamy cells, and restrained the hyperplasia of smooth muscle cells in aorta wall. Conclusion ： Formononetin can modify lipid metabolism in hypercholesterolemic hamsters by reducing TC, TG and LDL-C, increasing HDL- C, and attenuating hepatic lipogenesis and atherosclerosis. Therefore, it may be a potential drug candidate or lead compound for anti-atherosclerosis through new targets.

关 键 词：刺芒柄花素 HDL受体/SR-BI蛋白 高通量药物筛选 高脂血症金黄地鼠 动脉粥样硬化 

分 类 号：R969.4[医药卫生—药理学]