补肾降脂方通过PPARγ-LXRα-ABCA1通路干预ApoE-/-小鼠动脉粥样硬化的效应机制  

Effect mechanism of Bushen Jiangzhi recipe on atherosclerosis in ApoE-/- mice through PPARγ-LXRα-ABCA1 Pathway

作　　者：贾庆玲 申定珠[1] JIA Qingling;SHEN Dingzhu(Shanghai Geriatrics Institute of Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200031,China)

机构地区：[1]上海中医药大学上海市中医老年医学研究所,上海200031

出　　处：《上海中医药杂志》2020年第4期85-91,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81873348);全国中医药创新骨干人才培训项目[国中医药人教函(2019)128号];上海中医药大学研究生“创新能力培养”专项研究项目(Y201858)

摘　　要：目的探讨补肾降脂方通过PPARγ-LXRα-ABCA1通路干预ApoE-/-小鼠动脉粥样硬化(AS)的效应机制。方法采用高脂饮食喂饲ApoE-/-小鼠复制AS模型,随机分为ApoE-/-小鼠+高脂饮食喂饲组(模型组)、ApoE-/-小鼠+高脂饮食喂饲+补肾降脂方组(补肾组)、ApoE-/-小鼠+高脂饮食喂饲+阿托伐他汀组(他汀组),同品系、同周龄雄性C57BL/6小鼠为正常对照组(正常组),每组25只。各组给予相应干预12周。HE、油红O染色法分别检测小鼠主动脉窦、肝脏组织病理形态及脂质蓄积,Filipin染色法检测小鼠主动脉窦游离胆固醇;ELISA法检测小鼠外周血血清脂质(TC、TG、LDL-C、HDL-C)含量;Western blot法检测小鼠主动脉、肝脏组织PPARγ、LXRα及ABCA1蛋白表达。结果高脂饮食喂饲的ApoE-/-小鼠呈典型的AS病变,主动脉窦可见大面积AS斑块及红染脂质,游离胆固醇增多;肝脏组织可见肝细胞结构紊乱,红染脂质蓄积;血清TC、LDL-C含量升高,HDL-C含量降低;主动脉及肝脏组织PPARγ、LXRα、ABCA1蛋白表达降低。与模型组比较,补肾组小鼠主动脉窦AS斑块面积、红染脂质、游离胆固醇均减少;肝脏组织肝细胞结构大部分清晰可见,红染脂质减少;血清TC、LDL-C含量降低;主动脉及肝脏组织PPARγ、LXRα、ABCA1蛋白表达上调。结论补肾降脂方可能通过调控PPARγ-LXRα-ABCA1通路进而有效干预治疗动脉粥样硬化。Objective To investigate the effect mechanism Bushen Jiangzhi recipe on atherosclerosis(AS)in ApoE-/-mice by regulating PPARγ-LXRα-ABCA1 pathway.Methods ApoE-/-mice with high-fat diet were randomly divided into three groups:ApoE-/-mice+high-fat diet group(model group),ApoE-/-mice+high-fat diet+Bushen Jiangzhi recipe group(Bushen group),and ApoE-/-mice+high-fat diet+Atorvastatin group(statin group).Male C57 BL/6 mice of the same age and strain were used as normal control group(normal group)fed with common diet with 25 mice in each group.Each group was given corresponding intervention for 12 weeks.HE and Oil Red O staining were performed to detect pathological morphology and lipid accumulation of mouse aortic sinus and liver tissues respectively,and Filipin staining was performed to detect free cholesterol in mouse aortic sinus.Serum lipid levels(TC,TG,LDL-C,HDL-C)in peripheral blood of mice were detected by ELISA;The expression of PPARγ,LXRαand ABCA1 in aorta and liver tissues of mice was analyzed by Western blot.Results ApoE-/-mice fed with high-fat diet showed typical AS lesions,large area of AS plaque and red-stained lipid were seen in aortic sinus,and free cholesterol increased.Hepatocyte structure disorder and red-stained lipid accumulation can be seen in the liver tissue.The content of TC and LDL-C in serum increased while that of HDL-C decreased.The protein expression levels of PPARγ,LXRαand ABCA1 in aorta and liver tissues decreased.Compared with the model group,the area of AS plaque,red stained lipid and free cholesterol in aortic sinus of mice in Bushen group decreased.The structure of liver cells in liver tissue was mostly clearly visible,and red stained lipid reduced.The content of serum TC and LDL-C decreased.The protein expression levels of PPARγ,LXRαand ABCA1 in aorta and liver tissues were up-regulated after intervention by Bushen Jiangzhi recipe.Conclusion Bushen Jiangzhi recipe may effectively intervene the treatment of AS by regulating PPARγ-LXRα-ABCA1 pathway.

关 键 词：补肾降脂方 动脉粥样硬化 PPARγ-LXRα-ABCA1 

分 类 号：R285.5[医药卫生—中药学]