摘要
目的:基于核因子红系2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)轴探讨大黄黄连泻心汤加味对2型糖尿病(T2DM)大鼠肝脏氧化应激损伤的影响及其作用机制。方法:6只ZDF(fa/+)大鼠为正常组,30只ZDF(fa/fa)大鼠为造模组,采用高脂饲料喂食诱导建立T2DM大鼠模型,造模成功后随机分为模型组、二甲双胍组(0.18 g·kg^(-1))及大黄黄连泻心汤加味低、中、高剂量组(0.54、1.08、2.16 g·kg^(-1)),每组6只。药物干预12周后测定大鼠体质量、肝质量、空腹血糖(FBG)、口服葡萄糖耐量试验(OGTT)水平、全自动生化仪检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,苏木素-伊红(HE)染色观察肝脏组织病理形态变化,酶联免疫吸附测定法(ELISA)检测肝脏组织超氧化物歧化酶(SOD)、活性氧(ROS)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)水平,免疫组化检测肝脏Nrf2的表达,实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测肝脏组织Nrf2、HO-1 mRNA及蛋白表达水平。结果:与正常组比较,模型组大鼠体质量、肝质量、肝指数均显著升高(P<0.01);与模型组比较,二甲双胍组及大黄黄连泻心汤加味中、高剂量组大鼠体质量、肝质量、肝指数均显著降低(P<0.01)。与正常组比较,模型组大鼠TC、TG、LDL含量均显著升高(P<0.01),HDL含量显著降低(P<0.01);与模型组比较,二甲双胍及大黄黄连泻心汤加味各剂量组TC含量均显著降低(P<0.01),二甲双胍及大黄黄连泻心汤加味各剂量组TG含量均明显降低(P<0.05),大黄黄连泻心汤加味中、高剂量组LDL含量明显降低(P<0.05),二甲双胍及大黄黄连泻心汤加味各剂量组HDL含量明显升高(P<0.05)。与正常组比较,模型组大鼠ALT、AST活性显著升高(P<0.01);与模型组比较,二甲双胍及大黄黄连泻心汤加味�
Objective:To explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus(T2DM)rats based on the nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)axis.Method:Six ZDF(fa/+)rats were as assigned to the blank group,and 30 ZDF(fa/fa)rats were used to induce the T2DM model by feeding a high-fat diet.After successful modeling,the rats were randomly divided into the model group,metformin group(0.18 g·kg^(-1)),and low,medium,and high dose groups of modified Dahuang Huanglian Xiexintang(0.54,1.08,2.16 g·kg^(-1)),with six rats in each group.After 12 weeks of drug intervention,the body mass,liver mass,fasting blood glucose(FBG),and oral glucose tolerance test(OGTT)levels were measured.Serum total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL),low-density lipoprotein cholesterol(LDL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels were detected using an automatic biochemical analyzer.The pathological changes of liver tissue were observed by hematoxylin-eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect the activity of superoxide dismutase(SOD),reactive oxygen species(ROS),glutathione peroxidase(GSH-Px),and the level of malondialdehyde(MDA)in liver tissues.Immunohistochemistry was used to detect the expression of Nrf2 in the liver.Real time quantitative polymerase chain reaction(Real-time PCR)and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues.Result:Compared with the normal group,the model group showed a significant increase in body mass,liver mass,and liver index(P<0.01).Compared with the model group,the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight,liver mass,and liver index(P<0.01).Compared with the normal group,the model group showed significantly increased TC,TG,and LDL levels(P<0.01),and signi
作者
马成军
闫丰喆
杨丽霞
梁永林
朱向东
安冬
高艳奎
MA Chengjun;YAN Fengzhe;YANG Lixia;LIANG Yonglin;ZHU Xiangdong;AN Dong;GAO Yankui(Gansu University of Chinese Medicine,Lanzhou 730000,China;Shaoxing People's Hospital,Shaoxing 312035,China;Ningxia Medical University,Yinchuan 750004,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2024年第24期121-130,共10页
Chinese Journal of Experimental Traditional Medical Formulae
基金
甘肃省教育厅产业支撑项目(2021CYZC-03)
甘肃省优秀博士生项目(23JRRA1218)
国家自然科学基金项目(82060914)。
