硫化氢对2型糖尿病大鼠肝脏胰岛素抵抗的影响  

Effects of Hydrogen Sulfide on Liver Insulin Resistance of Type 2 Diabetic Rats

作　　者：高啸[1] 彭旖旎[1] 朱琳[1] 杨少娟[1] 胡军[1] 

机构地区：[1]华中科技大学同济医学院附属梨园医院内分泌科,武汉430077

出　　处：《华中科技大学学报（医学版）》2016年第5期490-495,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2012FFB02317)

摘　　要：目的研究硫化氢(Hydrogen sulfide,H_2S)对2型糖尿病大鼠肝脏胰岛素抵抗的影响。方法取雄性SD大鼠,采用高糖高脂饮食喂养和腹腔注射小剂量STZ的方法制作大鼠2型糖尿病模型,将成模后大鼠随机分为糖尿病组(DM组)、糖尿病+NaHS(H_2S供体)组(DM+NaHS组)、糖尿病+炔丙基甘氨酸(PAG,CSE的抑制剂)组(DM+PAG组),另设对照组,各15只。每日在固定的时间腹腔注射受试制剂,DM+NaHS组注射NaHS 56μmol/(kg·d),DM+PAG组给予PAG 50mg/(kg·d),对照组和DM组注射相同体积的生理盐水,连续给药2周后处死大鼠。分别检测各组空腹血糖、血浆胰岛素水平、肝脏组织中H_2S水平,苏木精-伊红染色观察各组肝脏组织病理学变化;免疫组化法检测胰岛素受体底物-2(IRS-2)的表达;Western blot和RT-PCR检测胱硫醚-γ-裂解酶(CSE)、胰岛素受体(InsR)和IRS-2的表达。结果与对照组相比,DM组空腹血糖水平升高、胰岛素水平明显下降,CSE表达明显升高,InsR、IRS-2表达明显降低(均P<0.05),肝小叶结构破坏,脂肪变性明显,有炎症细胞浸润;与DM组比较,DM+NaHS组空腹血糖水平明显升高(P<0.05),胰岛素水平、CSE、InsR、IRS-2表达明显降低(均P<0.05),肝组织病变更明显;与DM组比较,DM+PAG组空腹血糖水平、CSE表达明显降低(均P<0.05),而胰岛素水平、InsR、IRS-2表达明显升高(均P<0.05),肝组织病变有所减轻。结论 H_2S可通过下调2型糖尿病大鼠肝细胞InsR和IRS-2的表达水平,促进胰岛素抵抗;PAG可通过上调2型糖尿病大鼠肝细胞InsR和IRS-2的表达水平,改善胰岛素抵抗。Objective To examine the effects of hydrogen sulfide（H2S）on liver insulin resistance of rats with type 2 diabetes mellitus（T2DM）.Methods T2DM models were established in male SD rats by high-sugar high-fat diet and intraperitoneal injection of low-dose streptozotocin（STZ）.The model rats were randomly divided into 4 groups（n=15each）：DM group,DM＋NaSH（an H2S donor）group,DM＋DL-propargylglycine[PAG,an inhibitor of cystathionine-γ-lyse（CSE）]group（DM＋PAG group）,and normal control group.DM rats were intraperitoneally injected with NaSH 56μmol/（kg·d）and PAG 50mg（kg·d）in DM＋NaSH group and DM＋PAG group,respectively,and the same volume of normal saline was used in the DM and normal control groups.Two weeks later,the plasma levels of fasting blood glucose（FBG）and insulin,and H2S levels in liver tissues were measured.The pathological changes of the liver were observed by using HE staining.The protein expression levels of insulin receptor substrate-2（IRS-2）were detected by immunohistochemistry.The protein and mRNA expression levels of CSE,insulin receptor（InsR）and IRS-2 were determined by Western blotting and reverse transcription polymerase chain reaction（RTPCR）,respectively.Results The levels of FBG and the expression levels of CSE were significantly increased,and the levels of insulin and the expression levels of INSR and IRS-2 were profoundly decreased in DM group compared with normal control group.In T2DM rats,the structure of hepatic lobule was damaged,and there were obvious hepatic steatosis and interstitial inflammatory infiltration.The levels of FBG were significantly increased,and the level of insulin and the expression levels of CSE,InsR,and IRS-2were markedly decreased in DM＋NaHS group as compared with DM group.The damage of liver tissue was more obvious in DM＋NaHS group.Compared with DM group,the DM＋PAG group had a decrease in the levels of FBG and the expression levels of CSE.The insulin levels,and the expression levels of InsR and IRS-2were

关 键 词：2型糖尿病 硫化氢 炔丙基甘氨酸 胰岛素抵抗 胰岛素受体 胰岛素受体底物-2 

分 类 号：R587.1[医药卫生—内分泌]