依帕司他对2型糖尿病大鼠肝损伤的作用

发布时间：2018-04-09 03:00

本文选题：依帕司他　切入点：型糖尿病　出处：《首都医科大学学报》2017年02期

【摘要】：目的探讨依帕司他对2型糖尿病大鼠肝损伤的作用及机制。方法 SD大鼠经高糖高脂饮食喂养联合腹腔注射45mg·kg-1链脲佐菌素(Streptozotocin,STZ)建立2型糖尿病大鼠模型,将造模成功的大鼠分为模型对照组,依帕司他组(100 mg·kg-1)。另取12只正常SD大鼠设为正常对照组。依帕司他组连续8周灌胃给药,模型对照组和正常对照组给予0.5%(质量分数)羧甲基纤维素钠。观察依帕司他对2型糖尿病大鼠体质量、进食饮水量、血糖、血脂、肝功能、肝脏组织学及氧化应激反应的影响,并采用免疫组织化学方法检测肝脏组织中α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达。结果与模型对照组比较,给药8周后,依帕司他组大鼠空腹血糖和血脂降低,氧化应激反应降低,肝功能明显改善。病理学检查结果表明伊帕司他组大鼠肝脏炎性反应和纤维化病变较模型对照组减轻。免疫组织化学结果可见依帕司他组大鼠肝组织α-SMA和TGF-β1表达显著低于模型对照组。结论依帕司他能够提高机体抗氧化能力,改善2型糖尿病大鼠氧化应激肝损伤,并且能够通过抑制肝星状细胞(hepatic stellate cell,HSC)的激活改善糖尿病大鼠肝纤维化。
[Abstract]:Objective to investigate the effect and mechanism of epalrestat on liver injury in type 2 diabetic rats.Methods SD rats were fed with high glucose and high fat diet combined with intraperitoneal injection of 45mg kg-1 streptozotocin (STZ) to establish the model of type 2 diabetes mellitus. The successful rats were divided into model control group and epalestat group (100mg 路kg ~ (-1)).Another 12 normal SD rats were selected as normal control group.For 8 weeks, the model group and the normal control group were given 0.5% sodium carboxymethyl cellulose.To observe the effects of epalrestat on body mass, intake and drinking water, blood glucose, blood lipid, liver function, liver histology and oxidative stress in type 2 diabetic rats.The expression of 伪 -smooth muscle actin (伪 -SMA-1) and transforming growth factor- 尾 1(transforming growth factor- 尾 1 (TGF- 尾 1) in liver tissues were detected by immunohistochemical method.Results compared with the model control group, after 8 weeks of administration, the fasting blood glucose, blood lipid, oxidative stress and liver function were significantly improved in the Eparastatin group.Pathological examination showed that the inflammatory reaction and fibrosis of liver in Ipastatin group were less than those in model control group.Immunohistochemical results showed that the expression of 伪 -SMA and TGF- 尾 1 in the liver tissue of the Eparinast group was significantly lower than that of the model control group.Conclusion Eparrilast can improve the antioxidant ability and liver injury of type 2 diabetic rats under oxidative stress, and can improve hepatic fibrosis by inhibiting the activation of hepatic stellate cells (HSC) in diabetic rats.
【作者单位】：广东药科大学中药学院;中国医学科学院药物研究所靶点研究与新药筛选北京市重点实验室;
【基金】：“重大新药创制”科技重大专项(2013ZX09508104)~~
【分类号】：R587.2;R575

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