黄连素对2型糖尿病大鼠肝脏Nrf2介导的氧化应激反应的影响

Effects of berberine on Nrf2 mediated oxidative stress in liver of type 2 diabetic rats

目的:观察黄连素对2型糖尿病(T2DM)大鼠肝脏氧化损伤的保护作用,并探讨其作用机制。方法:采用高脂饲料加低剂量链脲佐菌素(STZ)建立T2DM大鼠模型,将其随机分为模型组和黄连素组,同性别、周龄的未造模动物作为正常组。连续灌胃给药20周,实验结束时检测肝重指数、血糖、超氧化物歧化酶(SOD)及丙二醛(MDA)水平。Real-time PCR检测转录因子NF-E2相关因子2(Nrf2)、Kelch样环氧氯丙烷相关蛋白1(Keap1)、SOD、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、血红素氧合酶1(HO1)mRNA表达。免疫组化和Western Blot检测Nrf2、Keap1、SOD、CAT、GSH-Px、HO1蛋白的表达情况。结果:黄连素可降低模型大鼠的肝重指数和MDA水平(P<0.05),升高SOD活性(P<0.05),显著上调肝脏中Nrf2、SOD、CAT、GSH-Px、HO1 mRNA及蛋白水平的表达(P<0.01,P<0.05)。结论:黄连素可对T2DM大鼠的肝脏具有保护作用,其作用机制可能是通过Nrf2介导的抗氧化来实现的。

Objective:To observe the protective effect of berberine on liver oxidative damage in rats with type 2 diabetes mellitus (T2DM) and to explore its mechanism.Methods:T2DM rat model was established by adding high-fat feed and low-dose streptozotocin (STZ),which was randomly divided into model group and berberine group.The animals of the same sex and week age were regarded as the normal group.All rats were administrated by gavage for 20 weeks,at the end of the experiment,liver weight index,blood glucose,SOD and MDA levels were measured.The mRNA expressions of Nrf2,Keap1,SOD,CAT,GSH-Px and HO1 were detected by Real-time PCR.Expressions of Nrf2,Keap1,SOD,CAT,GSH-Px and HO1 were detected by immunohistochemistry and Western Blot.Results:Berberine could reduce the liver weight index and MDA level of the model rats (P<0.05),increase the SOD activity (P<0.05),and significantly increase the mRNA and protein levels of Nrf2,SOD,CAT,GSH-Px and HO1 in the liver (P<0.01,P<0.05).Conclusion:Berberine has a protective effect on the liver of T2DM rats,and its mechanism may be realized by Nrf2 mediated antioxidant reaction.