本文選題：依帕司他　切入點(diǎn)：型糖尿病　出處：《首都醫(yī)科大學(xué)學(xué)報(bào)》2017年02期

【摘要】：目的探討依帕司他對(duì)2型糖尿病大鼠肝損傷的作用及機(jī)制。方法 SD大鼠經(jīng)高糖高脂飲食喂養(yǎng)聯(lián)合腹腔注射45mg·kg-1鏈脲佐菌素(Streptozotocin,STZ)建立2型糖尿病大鼠模型,將造模成功的大鼠分為模型對(duì)照組,依帕司他組(100 mg·kg-1)。另取12只正常SD大鼠設(shè)為正常對(duì)照組。依帕司他組連續(xù)8周灌胃給藥,模型對(duì)照組和正常對(duì)照組給予0.5%(質(zhì)量分?jǐn)?shù))羧甲基纖維素鈉。觀察依帕司他對(duì)2型糖尿病大鼠體質(zhì)量、進(jìn)食飲水量、血糖、血脂、肝功能、肝臟組織學(xué)及氧化應(yīng)激反應(yīng)的影響,并采用免疫組織化學(xué)方法檢測(cè)肝臟組織中α-平滑肌肌動(dòng)蛋白(α-smooth muscle actin,α-SMA)和轉(zhuǎn)化生長(zhǎng)因子-β1(transforming growth factor-β1,TGF-β1)表達(dá)。結(jié)果與模型對(duì)照組比較,給藥8周后,依帕司他組大鼠空腹血糖和血脂降低,氧化應(yīng)激反應(yīng)降低,肝功能明顯改善。病理學(xué)檢查結(jié)果表明伊帕司他組大鼠肝臟炎性反應(yīng)和纖維化病變較模型對(duì)照組減輕。免疫組織化學(xué)結(jié)果可見(jiàn)依帕司他組大鼠肝組織α-SMA和TGF-β1表達(dá)顯著低于模型對(duì)照組。結(jié)論依帕司他能夠提高機(jī)體抗氧化能力,改善2型糖尿病大鼠氧化應(yīng)激肝損傷,并且能夠通過(guò)抑制肝星狀細(xì)胞(hepatic stellate cell,HSC)的激活改善糖尿病大鼠肝纖維化。
[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 偽 -smooth muscle actin (偽 -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 偽 -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.
【作者單位】： 廣東藥科大學(xué)中藥學(xué)院;中國(guó)醫(yī)學(xué)科學(xué)院藥物研究所靶點(diǎn)研究與新藥篩選北京市重點(diǎn)實(shí)驗(yàn)室;
【基金】：“重大新藥創(chuàng)制”科技重大專(zhuān)項(xiàng)(2013ZX09508104)~~
【分類(lèi)號(hào)】：R587.2;R575

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