川芎嗪与氨基胍联合治疗对新生链脲佐菌素糖尿病大鼠肝功能的影响

摘要

目的:研究川芎嗪与氨基胍联合治疗对新生链脲佐菌素糖尿病大鼠(n0-STZ大鼠)肝功能的影响.方法:用出生当日Wistar大鼠腹腔注射链脲佐菌素复制n0-STZ大鼠模型.设立正常对照组、模型组、二甲双胍治疗组及川芎嗪+氨基胍联合治疗组.第32周检测空腹血糖(FPG)、空腹血浆胰岛素(FINS)、胰岛素抵抗指数(IRI)、血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性、肝组织中NO浓度、诱导型一氧化氮合酶(iNOS)活性及iNOS、caspase-3、Fas和Bcl-2蛋白的表达.结果:两组治疗均可以降低FPG及IRI,也可以降低肝组织NO浓度、iNOS活性及iNOS表达水平,改善肝功能,而联合治疗作用强于二甲双胍.与二甲双胍相比,联合治疗在降低肝组织caspase-3、Fas蛋白表达方面作用较强,在增加Bcl-2蛋白表达方面作用无显著差异.结论:川芎嗪+氨基胍联合治疗和二甲双胍单独治疗都能抑制iNOS活性,降低iNOS、caspase-3及Fas蛋白表达,增加Bcl-2蛋白表达,从而改善肝脏功能,但川芎嗪与氨基胍联合治疗保护肝功能的作用优于二甲双胍.%AIM:To investigate the effects of tetrmethylpyrazine combined with aminoguanidine on hepatic functions and expression of apoptosis-related proteins in neonatal-0 streptozocin (STZ)-induced (n0-STZ) diabetic rats.METHODS:Neonatal Wistar rats were intraperitoneally injected with a single dose of STZ to establish n0-STZ rt model.The n0-STZ rats were divided into 4 groups:normal control group,model group,mefformin treatment group and tetramethylpyrazine + aminoguanidine treatment group (combined therapy group).Fasting plasma glucose (FPG),fasting insulin (FINS),insulin resistance index (IRI),serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)were measured at the 32nd week.Nitric oxide (NO) concentration,inducible nitric oxide synthase (iNOS) activity,and protein expression levels of iNOS,caspase-3,Fas and Bcl-2 in hepatic tissues were also analyzed.RESULTS:Treatment with mefformin or combined therapy not only attenuated the increases in IRI and FPG,but also decreased the elevated serum levels of ALT and AST.Both treatments reduced NO concentration,iNOS,caspase-3 and Fas activity,and the protein expression of iNOS in the rat livers as well.The effects of combined therapy on the above indexes were stronger than those of metformin treatment.Both treatments enhanced the expression of Bcl-2 in the rt livers,and both effects had no difference.CONCLUSION:Tetrmethylpyrazine combined with aminoguanidine improves hepatic functions by ameliorating impaired Bcl-2 expression and decreasing the expression levels of caspase-3 and Fas in the livers of n0-STZ ats,which has stronger efficacy than metformin.