三七皂苷R1上调miR-146a水平和减轻ApoE^(-/-)小鼠肝脏炎症损伤的研究  

Study of Notoginsenoside R1 Relieving Liver Inflammatory Injury by Up-regulating miR-146a Level in ApoE^(-/-) Mice

作　　者：周兴宏[1] 刘晓瑜[1] 温子云[1] 何泽淮 程赛博[1] 张宇[1] 赵丹丹[1] 苏志杰[1] 周凤华[1] 贾钰华[1] 

机构地区：[1]南方医科大学中医药学院,广东广州510515

出　　处：《中药新药与临床药理》2016年第3期317-321,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81373574;81403339);广东省自然科学基金博士启动项目(2014A030310150);广东省中医药管理局科研项目(20141186);南方医科大学科研启动计划项目(PY2013N014)

摘　　要：目的观察三七皂苷R1(R1)对ApoE^(-/-)小鼠肝脏白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和微小RNA-146a(miR-146a)的影响。方法采用高脂饲料喂养雄性ApoE^(-/-)小鼠,建立小鼠动脉粥样硬化(Atherosclerosis,AS)模型,随机分为模型组,R1低、中、高剂量组,辛伐他汀组,另设同龄C57BL/6J雄性小鼠为正常对照组。连续给药12周后处死小鼠,检测血糖、血脂、肝功能(AST,ALT)以及肝匀浆TNF-α、IL-6等指标,HE染色观察肝组织病理形态学,PCR测肝脏miR-146a表达。结果模型组小鼠血糖、血脂、ALT、AST、TNF-α、IL-6均较正常对照组显著升高(P<0.05,P<0.01),血清HDL-C含量显著降低(P<0.01),肝脏切片可见小鼠肝细胞质内充满脂滴,大部分肝细胞呈现脂肪变性;与模型组比较,R1高剂量组能显著降低小鼠空腹血糖、血脂、AST、ALT以及肝脏中的TNF-α、IL-6(P<0.01),同时升高HDL-C和miR-146a水平(P<0.01);R1各组小鼠肝脂肪变性较模型组有所减轻。结论三七皂苷R1能降低AS小鼠血糖、血脂水平,并保护肝功能,其机制可能主要与三七皂苷R1升高肝脏miR-146a水平,降低TNF-α、IL-6等炎症因子有关。Objective To observe the effect of notoginsenoside R1 on the hepatic levels of interleukin- 6（IL- 6）,tumor necrosis factor（TNF-α） and miR- 146 a in atherosclerosis Apo E-/- mice. Methods Male ApoE^（-/-） mice were fed with high fat diet to induce atherosclerosis（AS） model,and then 50 male Apo E-/- mice were randomly divided into model group,simvastatin group,and low-,medium- and high- dose notoginsenoside R1 groups. Another 10 C57BL/6J mice were used for normal control. After medication for 12 continous weeks, all of the mice were sacrificed. The levels of blood glucose, blood lipids, serum aspartate aminotransferase（AST）, alanine aminotransferase（ALT） and high- density lipoprotein cholesterol（HDL- C）as well as the hepatic IL- 6 and TNF- α were measured by ELISA assay.The pathohistological changes in liver tissue were observed after hematoxylin and eosin staining. PCR was used for the detection of miR- 146 a expression. Results The levels of blood glucose, blood lipids, ALT, AST, IL- 6, and TNF- α in the model group were much higher than those in the normal control group（P〈0.05）,while HDL- C was significantly decreased in the model group（P〈0.01）. Liver cells of the model group were full of lipid droplet, and most of the liver cells presented fatty degeneration. High- dose notoginsenoside R1 could down- regulate blood glucose,blood lipids,AST,ALT,IL- 6,and TNF- α（P〈0.05）,and up- regulate the levels of HDL- C and miR- 146a（P〈0.01）. Furthermore,notoginsenoside R1 could alleviate the liver injury in AS mice. Conclusion Notoginsenoside R1 can down- regulate the levels of blood glucose and blood lipids,and protect the liver function. The mechanism may be related to up- regulating the expression of miR- 146 a and down- regulating the levels of IL- 6 and TNF- α in atherosclerosis mice.

关 键 词：三七皂苷R1 血脂 炎症因子 肝功能 MIR-146A 

分 类 号：R285.5[医药卫生—中药学]