茵栀黄联合罗格列酮对非酒精性脂肪肝大鼠的保护作用  

Protective Effects of Yinzhihuang Combined with Rosiglitazone on Nonalcoholic Fatty Liver Disease in Rats

作　　者：姚臻[1] 李家妮 张可锋[2] 郭丹 莫雨微 高雅[2] Yao Zhen;Li Jiani;Zhang Kefeng;Guo Dan;Mo Yuwei;Gao Ya(Nanxishan Hospital,Guangxi Zhuang Autonomous region,Guilin 541002;Guilin Medical University,Guilin 541004)

机构地区：[1]广西壮族自治区南溪山医院,桂林541002 [2]桂林医学院,桂林541004

出　　处：《中药药理与临床》2020年第2期171-175,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广西壮族自治区教育厅八桂学者专项经费项目[编号:桂财教函(2017)143号];广西壮族自治区卫生厅项目(编号:Z2015215)。

摘　　要：目的:探讨茵栀黄联合罗格列酮对非酒精性脂肪肝(NAFLD)大鼠的保护作用及作用机制。方法:将56只大鼠随机均分为正常对照组、模型对照组、茵栀黄9 g/kg组、罗格列酮2 mg/kg组、茵栀黄联合罗格列酮(4.5 g/kg+1 mg/kg)组,除正常对照组和模型对照组各13只外,其余每组10只。正常对照给予普通饲料,其余各组给予高糖高脂饲料(10 g/只)持续13 w,从第5 w开始给药,按5 ml/kg灌胃给药8 w。末次给药后禁食不禁水16 h,摘取眼球取血,取出肝脏,采用苏木精-伊红(HE)染色观察大鼠肝脏组织病理学改变,用生化法测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)含量或活性,酶联免疫吸附试验(ELISA)法检测肝脏中白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量和血清空腹胰岛素(FINS)含量,生化法测定血清中总胆固醇(TC)、低密度脂蛋白(LDL-c)、高密度脂蛋白(HDL-c)、甘油三酯(TG)的含量,血糖仪测定大鼠空腹血糖(FBG)含量;根据FINS和FBG计算胰岛素抵抗指数(HOMA-IR)。结果:与正常对照组比较,模型对照组大鼠肝脏切片观察到明显的脂肪变性和弥漫性脂滴空泡,血清中ALT、AST和MDA的活性或含量显著升高,SOD和GSH-Px的活性显著降低,肝组织中TNF-α、IL-1β和IL-6含量显著升高,血清中TC、TG显著增加,胰岛素抵抗指数(IRI)显著升高(P<0.01);与模型对照组比较,茵栀黄9 g/kg组、罗格列酮2 mg/kg组及茵栀黄联合罗格列酮(4.5 g/kg+1 mg/kg)组大鼠肝组织脂肪变、肝内脂肪空泡和炎性损伤、炎症细胞浸润都有不同程度改善,其中茵栀黄联合罗格列酮(4.5 g/kg+1 mg/kg)组改善程度最为明显,ALT、AST、MDA、TNF-α、IL-1β、IL-6、TC、TG和LDL-c的活性或含量均有不同程度的下降;HDL-c、SOD和GSH-Px的含量活性均升高;FBG、FINS和IRI均显著下降(P<0.05或P<0.01)。结论:在剂量减半情�Objective: To investigate the protective effect and mechanism of Yin Zhi Huang combined with rosiglitazone on nonalcoholic fatty liver(NAFLD) in rats. Methods: 56 rats were randomly divided into the control group,the model group, Yin Zhi Huang Group(9 g/kg), Rosiglitazone Group(2 mg/kg), and combination group(yin Zhi Huang4.5 g/kg +1 mg/kg rosiglitazone). There were 13 rats in the model group and control group, while 10 rats in other groups. Rats in the control group were given ordinary diet,those in other groups were given high sugar high fat diet(10 g/rats),for 13 weeks. Drugs were orally given at a dose of 5 ml/kg, from 5 th week, and lasted for 8 weeks. After the last administration, rats fasting but drinking water for 16 h, blood was taken from the eyeball,liver tissues were collected. Histopathological changes of liver tissues were detected by HE staining, the contents or activities of serum alanine aminotransferase(ALT), Straw transaminase(AST), malonaldehyde(MDA), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined by biochemical method. The contents of Interleukin-1β(IL-1β), Interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) in the liver tissue and FINS in serum were detected by ELISA. The contents of total cholesterol(TC), low-density lipoprotein(LDL-c), high-density lipoprotein(HDL-c) and triglyceride(TG) in serum were determined by biochemistry. The fasting blood glucose(FBG)of rats were determined by fast glucose analyzer, then the insulin resistance index was calculated by FINS and FBG(HOMA-IR). Results: Compared with the control group, the rats in the model group showed obvious fatty degeneration and diffuse lipid vacuoles, the activities or contents of ALT, AST and MDA in serum were significantly increased, the activities of SOD and GSH-Px were decreased, the contents of TNF-α, IL-1β and IL-6 in liver tissues were significantly increased,the serum levels of TC and TG were significantly increased,and insulin resistance index was elevated(P<0.01). Compared with

关 键 词：茵栀黄 罗格列酮 非酒精性脂肪肝 脂质代谢 氧化应激 炎症反应 

分 类 号：R575.5[医药卫生—消化系统]