茵栀黄联合二甲双胍对非酒精性脂肪肝大鼠的保护作用和机制研究  

Protective Effect and Mechanism of Yinzhihuang Combined with Metformin on Nonalcoholic Fatty Liver Disease in Rats

作　　者：葛鹏飞 李剑桥 高雅[2] 汪嘉康 闫婷 徐杰 张可锋[2] 钟明利[2] Ge Pengfei;Li Jianqiao;Gao Ya;Wang Jiakang;Yan Ting;Xu Jie;Zhang Kefeng;Zhong Mingli(The Second Affiliated Hospital of Guilin Medical College Guilin Medical University)

机构地区：[1]桂林医学院第二附属医院,桂林541004 [2]桂林医学院,桂林541199

出　　处：《中药药理与临床》2021年第2期150-155,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广西八桂学者专项项目(桂财教函[2017]143号)。

摘　　要：目的:探讨茵栀黄联合二甲双胍对非酒精性脂肪肝(NAFLD)大鼠的保护作用及机制。方法:将54只雄性SD大鼠随机分为2组,其中正常对照组(12只)和高脂饲料组(42只),进行NAFLD建模。8 w后每组随机各抽取2只,经病理检查确定NAFLD建模成功后,再将高脂饲料组随机分为模型对照组、茵栀黄9 g/kg组、二甲双胍0.2 g/kg组、茵栀黄联合二甲双胍(4.5 g/kg+0.1 g/kg)组,每组10只。除了正常对照组及模型对照组以外,其他各组同时给予相应治疗药物,每天1次,连续5 w,末次给药后禁食不禁水16 h,取血液和肝脏。采用生化法检测血清中门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)以及肝组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力;酶联免疫吸附法(ELISA)检测肝组织中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)以及转化生长因子-β(TGF-β)的水平;蛋白质印迹法(Western blot)检测大鼠肝组织中过氧化物酶增殖物激活受体-α(PPAR-α)蛋白的表达情况。苏木精-伊红(HE)染色观察肝组织病变程度。结果:与正常对照组比较,模型对照组大鼠血清中ALT、AST活性、TC、TG、LDL-C含量以及肝组织中MDA的含量显著升高(P<0.01);血清中HDL-C以及肝组织中SOD、GSH-Px的活力显著降低(P<0.01);肝组织中TNF-α、IL-6以及TGF-β含量均显著升高(P<0.01);肝组织中PPAR-α蛋白表达水平显著下调(P<0.01)。与模型对照组比较,各给药组大鼠以上指标均呈现不同程度的改善(P<0.05或P<0.01),其中茵栀黄联合二甲双胍组(4.5 g/kg+0.1 g/kg)改善程度最为明显。结论:茵栀黄和二甲双胍对NAFLD大鼠均具有治疗作用,并且联合应用二者的疗效明显优于单独应用茵栀黄或二甲双胍,其机制很可能与调节PPAR-α信号通路有关。Objective: To investigate the protective effect and mechanism of Yinzhihuang combined with metformin on non-alcoholic fatty liver(NAFLD) in rats. Methods: 54 male SD rats were randomly divided into 2 groups, including the control group(12 rats) and the high-fat diet group(42 rats) for the establishment of NAFLD model. After 8 weeks, 2 rats were randomly selected from each group. After the establishment of NAFLD model was proved successful by pathological examination, the rats in high-fat diet groups were randomly divided into the model group, 9 g/kg Yinzhihuang group, 0.2 g/kg metformin group, Yinzhihuang combined with metformin(4.5 g/kg+0.1 g/kg) group, 10 rats in each group. Except for the control group and the model group, the rats in the other groups were given corresponding drugs at the same time, once a day for 5 weeks, after the last administration, rats were fasted for 16 hours. Blood and liver tissues were collected. The contents or activities of serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C), high-density lipoprotein(HDL-C) and liver tissue malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione Peroxidase(GSH-Px) were detected by biochemical methods. The contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and transforming growth factor-β(TGF-β) in liver tissues were determined by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of peroxidase proliferator-activated receptor-α(PPAR-α) protein in rat liver tissue. Hematoxylin-Eosin(HE) staining was used to observe the pathological changes of liver tissues. Results: Compared with the control group, the serum contents of ALT, AST, TC, TG, LDL-C and MDA in the model group were significantly increased(P<0.01), the serum contents of HDL-C,SOD and GSH-Px were significantly decreased(P<0.01), the liver tissue contents of TNF-α, IL-6 and TGF-β were significantly increased(P<0.01), the PPAR-α protein ex

关 键 词：茵栀黄 二甲双胍 非酒精性脂肪肝 过氧化物酶增殖物激活受体-α信号通路 

分 类 号：R965[医药卫生—药理学]