Nrf2对高脂饮食诱导的大鼠胰岛素抵抗的保护作用

目的研究姜黄素诱导大鼠肝脏转录因子NF-E2相关因子2(Nrf2)核转位对高脂饮食诱导的大鼠胰岛素抵抗(IR)的保护作用及机制。方法雄性SD大鼠24只随机分为对照组、模型组和干预组,每组8只。对照组给予正常饮食,模型组及干预组均给予髙脂饮食。6周末行胰岛素-正常血糖钳夹术检测各组大鼠IR。之后模型组继续髙脂饮食,干预组予髙脂饮食加姜黄素灌胃200 mg/(kg.d),共4周。第10周末处死所有大鼠观察肝脏病理学变化,检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT),分光光度法检测丙二醛(MDA)、谷胱甘肽(GSH)水平,Western blot检测肝脏Nrf2、胰岛素受体底物-1(IRS-1)、jun N-末端激酶(JNK)、p-JNK及p-IRS-1水平。结果姜黄素干预组大鼠肝脏Nrf2的核转位较其他组明显增加;模型组MDA、AST、ALT较对照组显著升高(P<0.01),干预组MDA、AST、ALT较模型组显著降低(P<0.01);模型组GSH较对照组显著降低(P<0.01),干预组GSH较模型组显著升高(P<0.01)。Western blot结果显示,与模型组比较,干预组Nrf2核转位增加、p-JNK水平降低、p-IRS-1水平增加、JNK及IRS-1水平无明显变化。结论诱导Nrf2核转位能够减轻大鼠肝脏氧化应激损伤,进而改善肝脏的胰岛素抵抗。

Protective effect of Nrf2 on the high fat diet-induced insulin resistance in rats

Objective To investigate the protective effect of nuclear factor E2-related factor 2(Nrf2) nuclear translocation on the high fat diet induced-insulin resistance in rats and to explore its possible mechanism.Methods Twenty-four male SD rats were randomized into 3 groups:control group(n=8),model group(n=8) and curcumine-treated group(n=8).Rats were given normal diet in control group,and high fat diet in the other groups.IR models were validated with hyperinsulinemic-euglycemic clamp test in model group and co...