黄连素通过PPARγ-LXRα-ABCA1信号通路促进ApoE^(-/-)小鼠胆固醇代谢的作用机制研究  

Effect of Berberine on Cholesterol Metabolism in ApoE^(-/-) Mice through PPARγ-LXRα-ABCA1 Signaling Pathway

作　　者：李智 高铸烨[2] 别玉龙[2] 陈鑫 白瑞娜 LI Zhi;GAO Zhuye;BIE Yulong;CHEN Xin;BAI Ruina(School of Clinical Medicine,Beijing University of Chinese Medicine,Beijing 100105,China;National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]北京中医药大学临床医学院,北京100105 [2]国家中医心血管病临床医学中心,中国中医科学院西苑医院,北京100091

出　　处：《中华中医药学刊》2022年第10期28-32,I0012,I0013,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家重点研发计划(2019YFC1710303);国家自然科学基金青年科学基金(81603489);中国中医科学院优秀青年科技人才(创新类)培养专项(ZZ13-YQ-005)。

摘　　要：目的观察黄连素对高脂饮食诱导的ApoE小鼠胆固醇代谢的调节效应及作用机制。方法8周龄SPF级雄性ApoE^(-/-)小鼠40只,随机分为模型组、黄连素小剂量组(50 mg·kg^(-1)·d^(-1))、黄连素大剂量组(100 mg·kg^(-1)·d^(-1))、阿托伐他汀组(10 mg·kg^(-1)·d^(-1));同源C57/BL6小鼠10只作为正常组。模型组和正常组给予等体积0.5%羧甲基纤维素钠灌胃。12周后检测血脂、肝功能、氧化应激、脂质过氧化,肝脏切片进行油红O和HE染色,Western blot检测PPARγ、LXRα、ABCA1蛋白表达。结果与正常组相比,模型组小鼠总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)水平升高明显升高,高密度脂蛋白胆固醇(HDL-C)显著下降(P<0.05);与模型组相比,黄连素组和阿托伐他汀组TC和LDL-C明显下降,黄连素大剂量组及阿托伐他汀组HDL-C显著升高,黄连素剂量依赖性降低ALT、AST、AKP水平(P<0.05),但阿托伐他汀对ALT、AST、AKP降低不明显(P>0.05)。与正常组相比,模型组小鼠肝脏细胞中有明显脂肪沉积和大量脂滴形成,同时肝细胞排列紊乱;黄连素和阿托伐他汀治疗后好转。与正常组相比,模型组丙二醛(MDA)升高,总超氧化物歧化酶(SOD)及一氧化氮(NO)下降(P<0.05);与模型组相比,黄连素组和阿托伐他汀组MDA显著下降,总SOD及NO显著升高(P<0.05)。Western blot结果提示,与正常组相比,模型组PPARγ、LXRα、ABCA1蛋白表达下降(P<0.05);与模型组相比,黄连素组呈剂量依赖性上调PPARγ、LXRα、ABCA1蛋白表达(P<0.05)。结论黄连素可能通过PPARγ-LXRα-ABCA1信号通路改善高脂饮食诱导的ApoE小鼠血脂代谢紊乱,从而减轻氧化应激反应及脂质过氧化损伤,抑制肝脏细胞内脂肪积累,减轻肝细胞损伤。Objective To observe the regulatory effect and mechanism of berberine on cholesterol metabolism induced by high fat diet in ApoE^(-/-)mice.Methods Forty 8-week-old SPF male ApoEmice were randomly divided into model group,low-dose berberine group(50 mg·kg^(-1)·d^(-1)),high-dose berberine group(100 mg·kg^(-1)·d^(-1))and atorvastatin group(10 mg·kg^(-1)·d^(-1)).Ten C57/BL6 mice were used as the normal group.The model group and the normal group were given equal volume of 0.5%sodium carboxymethyl cellulose(CMC)by gavage.After 12 weeks,the blood lipid,liver function,oxidative stress and lipid peroxidation were detected.Liver sections were stained with oil red O and HE staining methods,and the expressions of peroxisome proliferators-activated receptorγ(PPARγ),liver X receptorα(LXRα)and ATP-binding cassette transporter A1(ABCA1)were detected by Western blot.Results Compared with those of the normal group,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alkaline phosphatase(AKP)in the model group increased significantly,while the level of high density lipoprotein cholesterol(HDL-C)was decreased significantly(P<0.05).Compared with those of the model group,the levels of TC and LDL-C in berberine groups and atorvastatin group were decreased significantly,the levels of HDL-C in high-dose berberine group and atorvastatin group were increased significantly,and the levels of ALT,AST and AKP decreased in a dose-dependent manner of berberine(P<0.05),but the lowering effect of atorvastatin on ALT,AST and AKP was not obvious(P>0.05).Compared with the normal group,there was obvious fat deposition and a large number of lipid droplets in the liver cells,and the liver cells were disordered in the model group.Berberine and atorvastatin improved after treatment.Compared with the normal group,the level of malonaldehyde(MDA)was increased,the levels of total superoxide dismutase(SOD)and nitrous oxide(NO)were decreased in

关 键 词：黄连素 脂质代谢 氧化应激 脂质过氧化 肝脏脂肪沉积 

分 类 号：R285.5[医药卫生—中药学]