化瘀祛痰方药对动脉粥样硬化模型小鼠肝脏胆固醇代谢相关基因表达调控的影响  

Effect of Huayu Qutan Recipe on the metabolism of cholesterol in ApoE-/-atherosclerotic mice

作　　者：贾连群[1] 陈文娜[1] 赵秋宇[1] 杜莹[1] 杨关林[1] 

机构地区：[1]辽宁中医药大学省部共建中医脏象理论及应用教育部重点实验室,沈阳110032

出　　处：《中华中医药杂志》2014年第1期214-218,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重点基础研究发展计划(973计划)项目(No.2013CB531704);国家自然科学基金青年基金项目(No.81202834);沈阳市科技计划项目(No.F12-277-1-49)~~

摘　　要：目的:观察化瘀祛痰方药对ApoE基因敲除(ApoE-/-)动脉粥样硬化(AS)模型小鼠肝脏胆固醇合成、摄取和转化相关基因的影响,探讨化瘀祛痰方药抗AS作用及可能的机制。方法:20只ApoE-/-小鼠随机分为模型组、化瘀祛痰组(20g·kg-1·d-1),10只C57BL/6/J小鼠作为空白对照。ELISA法检测小鼠血清载脂蛋白A(ApoA)、载脂蛋白B100(ApoB100)含量,全自动生化分析仪检测血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,HE染色观察小鼠主动脉及肝脏结构变化,油红O染色观察主动脉及肝脏脂质沉积,real-time RT-PCR和Western blotting法检测肝脏低密度脂蛋白受体(LDL-R)、胆固醇7α-羟化酶(CYP7A1)、B类Ⅰ型清道夫受体(SR-BⅠ)、3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGCR)基因mRNA和蛋白水平。结果:与空白对照组相比,模型组小鼠血清ApoB100、TC、TG、LDL-C水平显著升高,ApoA、HDL-C水平显著降低,主动脉管腔见较大粥样斑块,管壁和肝细胞中见大量脂质沉积,肝脏LDL-R、CYP7A1、SR-BⅠ、HMGCR基因表达显著下调。与模型组相比,化瘀祛痰组小鼠ApoB100、TC、TG、LDL-C显著下降,ApoA、HDL-C显著升高,主动脉管腔中粥样斑块面积和管壁脂质沉积量明显减少,肝脏LDL-R、CYP7A1、SR-BⅠ基因表达显著上调,HMGCR基因表达未见明显变化。结论:化瘀祛痰方药可抑制ApoE-/-小鼠主动脉斑块形成,其机制可能与调控肝脏胆固醇摄取和转化相关基因表达有关。Objective： Observation of the effects and mechanism of Huayu Qutan Recipe on the metabolism of cholesterol in ApoE-/- atherosclerotic mice, to illuminate the role and mechanism of Huayu Qutan Recipe on atherosclerosis. Methods： 10 normal C57BL/6/J mice were randomly divided into blank group. 20 ApoE-/- mice were divided randomly into model group and Huayu Qutan Recipe group （20g.kg 1.d-l）. The level of serum lipid was tested by biochemical methods. The aortic wall and liver injury of ApoE-/- atherosclerotic mice were observed by HE and oil red O staining method. The expression changes of LDL-R, CYP7A1, SR-B I and HMGCR were tested by RT-PCR and Western Blotting methods. Results： Compared with the blank group, the serum content of ApoB 100, TC, TG, LDL-C increased, while those of ApoA, HDL-C were significantly reduced, the aortic lumen see larger atheromatous plaque, a lot of lipid deposited in the tube wall and liver cells, while the mRNA and protein levels of LDL-R, CYP7A1, SR-B I and HMGCR in liver were decreased significantly in the model group. In Huayu Qutan Recipe group, the serum content of ApoB 100, TC, TG and LDL-C were lower and ApoA, HDL-C were higher compared with the model group. The atherosclerotic of aortic lumen plaque area and tube wall lipid deposition were decreased, the level of mRNA and protein of LDL-R, CYP7A1, SR-B I in liver were increased significantly, while HMGCR gene expression was not obviously changed. Conclusion： Huayu Qutan Recipe could inhibit the formation of the atherosclerotic plaques, which might be related to theregulation of cholesterol uptake and transformation of the related gene expression.

关 键 词：化瘀祛痰方药 动脉粥样硬化 载脂蛋白E基因敲除小鼠 胆固醇 

分 类 号：R259[医药卫生—中西医结合]