普罗布考对动脉粥样硬化兔HDL功能的影响及其调控机制

目的观察普罗布考对动脉粥样硬化兔巨噬细胞、肝细胞HDL功能的影响,并进一步探讨普罗布考抗动脉粥样硬化的机制。方法18只新西兰大白兔随机分为:(1)正常对照组(n=6):给予普通饮食喂养;(2)动脉粥样硬化组(n=6):饲以高脂饲料;(3)普罗布考组(n=6):在饲以高脂饮食基础上给予普罗布考400mg/(kg·d)]。12周后取血以酶法测定血脂;利用流式细胞仪检测腹腔巨噬细胞、肝细胞细胞表面ABCA1、SR-BⅠ表达量;液闪计数仪检测其3H]胆固醇转出率。结果实验12周后,普罗布考组血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、非高密度脂蛋白(NHDL-C)水平明显下降。普罗布考上调动脉粥样硬化兔腹腔巨噬细胞及肝细胞ABCA1及SR-BⅠ蛋白质表达水平。普罗布考组腹腔巨噬细胞、肝细胞3H]胆固醇转出率较动脉粥样硬化组明显上升。结论虽然普罗布考降低HDL-C,但是其通过上调腹腔巨噬细胞、肝细胞SR-BⅠ及ABCA1的表达及增加其3H]胆固醇转出率,改善HDL功能,具有促进动脉粥样硬化兔胆固醇逆转运(RCT)作用。

The effect and mechanism of probucol on HDL function in atherosclerotic rabbits

Objective To analyze the effect of probucol on HDL function and the its anti-atherosclerosis mecha-nism in atherosclerotic rabbits.Methods Eighteen rabbits were randomly assigned into three groups:(1)control group (n=6):normal diet for 12weeks;(2)atherosclerotic group:cholesterol diet of 12 weeks;(3)probucol group:choles-terol diet plus probucol(400mg/(kg·d))for 12 weeks.Flow cytometry and liquid scintillation spectrometry were used to measure the expressions of ABCA1 and SR-B,and cholesterol efflux rates,respectively,in peritoneal maerophage and hepatocvtes.Results Compared with atherosclerotic group,the levels of serum total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)and non-high-density lipoprotein cho-lesterol(NHDL-C)in probucol group were significantly reduced.In peritoneal macrophages and hepatocytes,the ABCA1 and SR-BI expression and~3H]cholesterol efflux rates significantly increased in probucol group compared with that in ath-eroselerotic group.Conclusion Via up-regulating SR-Bl and ABCA1 expression and increasing cholesterol efflux rates in peritoneal macrophages and hepatocytes,probucol improves HDL function and reverse cholesterol transport(RCT).