罗格列酮联合还原型谷胱甘肽对NAFLD大鼠胰岛素及胰岛素信号转导相关蛋白的影响

The effect of rosiglitazone combined with reduced glutathione on insulin signaling related proteins in NAFLD rats

目的研究罗格列酮联合还原型谷胱甘肽对非酒精性脂肪性肝病(NAFLD)大鼠胰岛素以及胰岛素信号转导相关蛋白表达的影响。方法建立NAFLD大鼠模型,设计罗格列酮单独和联合还原型谷胱甘肽治疗组、模型组、正常对照组,应用HE染色、免疫组织化学、ELISA方法比较各组大鼠血清和胰腺组织中胰岛素以及胰岛素信号转导相关蛋白[胰岛素受体(IR)和胰岛素受体底物-2(IRS-2)]表达水平。结果模型组血清胰岛素水平较正常对照组明显上升(P<0.01),而IR和IRS-2水平明显下降(P<0.01);药物干预组胰岛素水平较模型组明显下降(P<0.05),罗格列酮组IR水平较模型组及联合用药组明显上升(P<0.05),但其他指标在药物组和模型组之间差异无统计学意义。模型组大鼠胰腺组织内胰岛素表达强度明显高于正常组(P<0.05),药物组胰岛素表达强度明显低于模型组(P<0.05),而IR、IRS-2表达强度则明显高于模型组(P<0.05),两药物组之间差异无统计学意义。结论NAFLD大鼠血清和胰腺组织内胰岛素I、R和IRS-2含量均发生明显变化,罗格列酮单独或联合还原型谷胱甘肽能明显下调血清及胰腺组织内胰岛素表达,同时不同程度提高血清或胰腺组织内IR和IRS-2含量,但联合用药未显示协同作用。

Objective To investigate the effect of rosiglitazone and reduced glutathione on insulin signaling proteins in rats with nonalcoholic fatty liver disease（NAFLD）.Methods NAFLD rats were produced.Rats were divided into four groups： rosiglitazone group,group of rosiglitazone combined with reduced glutathione,model group and normal group.The insulin signaling proteins in serum and pancreatic tissue including insulin,insulin receptor（IR） and insulin receptor substrate-2（IRS-2） were detected by means of hematoxylin-eosin（HE） staining,immunohistochemisty and ELISA and their content or intensity were compared among the above groups.Results The serum insulin level of model group increased obviously compared with normal group（P0.01）,but the concentration of IR and IRS-2 in model group decreased markedly（P0.01）;The serum insulin levels of drug intervention groups were down-regulated obviously（P0.05）;The serum IR level of rosiglitazone group increased evidently compared with model group and combined treatment group（P0.05）.The insulin expressing level in pancreas of model group was obviously higher than that of normal group（P0.05）;The insulin expressing levels of drug treatment groups were much lower than that of model group（P0.05）,but the levels of IR and IRS-2 in drug treatment groups were higher than that of model group（P0.05）.Conclusion The concentrations of insulin,IR and IRS-2 in sera and pancreas of NAFLD rats changed remarkably;Rosiglitazone alone or combined with reduced glutathione might down-regulate the insulin levels in sera and pancreatic tissue of model group and up-regulate,to some extent,the concentrations of IR and IRS-2 of model group,but there was no ooperative effect in combined treatment.