小陷胸汤加味方对2型糖尿病大鼠肝损伤的保护作用及其机制  

Protective effect of Modified Xiao-Xian-Xiong Decoction on liver injury in rats with type 2 diabete mellitus and its mechanism

作　　者：关敬 哈森 袁颢 陈颖 刘鹏举 刘智 姜爽 GUAN Jing;HA Shen;YUAN Hao;CHEN Ying;LIU Pengju;LIU Zhi;JIANG Shuang(Department of Pharmacology,School of Clinical Medicine,Changchun University of Traditional Chinese Medicine,Changchun 130117,China;Department of Preventive Medicine,School of Health Management,Changchun University of Traditional Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学临床医学院药理学教研室,吉林长春130117 [2]长春中医药大学健康管理学院预防医学教研室,吉林长春130117

出　　处：《吉林大学学报（医学版）》2023年第3期608-616,共9页Journal of Jilin University：Medicine Edition

基　　金：吉林省教育厅科学技术研究项目(JJKH20210968KJ);吉林省教育厅大学生创新创业训练计划项目(S202210199026);吉林省中医药管理局中医药科技项目(2021009)。

摘　　要：目的:探讨小陷胸汤加味方(MXD)对2型糖尿病(T2DM)大鼠肝损伤的保护作用,阐明其可能的作用机制。方法:50只大鼠采用高糖高脂饲料喂养并联合链脲佐菌素(STZ)腹腔注射构建T2DM大鼠模型,40只造模成功大鼠随机分为模型组(不给予药物)、二甲双胍组(给予200 mg·kg^(-1)二甲双胍)、低剂量MXD组(给予630 mg·kg^(-1)MXD)和高剂量MXD组(给予1260 mg·kg^(-1)MXD),每组10只;另取10只大鼠作为对照组(给予标准饲料)。称量各组大鼠体质量,检测各组大鼠空腹血糖(FBG)水平,全自动生化分析仪检测各组大鼠血清中丙氨酸氨基转氨酶(ALT)和天冬氨酸氨基转氨酶(AST)活性,HE染色观察各组大鼠肝组织病理形态表现,酶联免疫吸附测定(ELISA)法检测各组大鼠血清中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平,分光光度计检测各组大鼠肝组织中超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)及丙二醛(MDA)水平,Western blotting法检测各组大鼠肝组织中核因子E2相关因子2(Nrf2)和血红素加氧酶(HO-1)蛋白表达水平。结果:对照组大鼠摄食和摄水量适中,均无骤增和骤减情况;模型组大鼠在注射STZ溶液后出现糖尿病的典型症状;与模型组比较,二甲双胍组、低剂量MXD组和高剂量MXD组大鼠糖尿病症状均有不同程度改善。与对照组比较,各时间点模型组大鼠体质量明显减小(P<0.01),FBG水平均明显升高(P<0.01);与模型组比较,给药第2、3和4周,二甲双胍组和高剂量MXD组大鼠FBG水平明显降低(P<0.01);给药第3和4周,低剂量MXD组大鼠FBG水平明显降低(P<0.05或P<0.01)。与对照组比较,模型组大鼠血清中AST和ALT活性均明显升高(P<0.01);与模型组比较,二甲双胍组、低剂量MXD组和高剂量MXD组大鼠血清中ALT和AST活性明显降低(P<0.01)。HE染色,对照组大鼠肝细胞形态正常,未见炎症细胞浸润;模型组可见严重的炎症细胞浸润状态;二Objective:To discuss the protective effect of Modified Xiao-Xian-Xiong Decoction(MXD)on liver injury in the rats with type 2 diabetes mellitus(T2DM),and to clarify its possible mechanism.Methods:Fifty rats were fed with high sugar and high fat combined with intraperitoneal injection of streptozotocin(STZ)to establish the T2DM rat models.A total of 40 rats successful modeling were randomly divided into model group(given no drugs),metformin group(given 200 mg·kg^(-1) metformin),low dose of MXD group(given 630 mg·kg^(-1) MXD),and high dose of MXD group(given 1260 mg·kg^(-1) MXD),and there were 10 rats in each group;another 10 rats were selected as control group(given standard feed).The body masses of the rats in various groups were detected;the fasting blood glucose(FBG)levels of the rats in various groups were detected;the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum of the rats in various groups were detected by fully automated biochemical analyzer;the pathomorphology of liver tissue of the rats in various groups were detected by HE staining;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factorα(TNF-α)in serum;the levels of superoxide dismutase(SOD),reductive glutathione(GSH),and malondialdehyde(MDA)in liver tissue of the rats in various groups were measured by spectrophotometer;the expression levels of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase(HO-1)proteins in liver tissue of the rats in various groups were detected by Western blotting method.Results:The rats in control group had moderate feeding and water intake,and the above indexes of the rats had no sudden increasing and decreasing;the rats in model group had typical symptoms of diabetes;compared with model group,the diabetes symptoms of the rats in meftormin group,low dose of MXD group,and high dose of MXD group had been improved to various degrees.Compared with control group,the body masses of the rats in model

关 键 词：小陷胸汤加味方 2型糖尿病 肝损伤 炎症反应 氧化应激 

分 类 号：R285.[医药卫生—中药学]