红景天苷改善糖尿病大鼠肝脏糖脂水平的作用机制

Mechanism of Salidroside in Improving Glucose and Lipid Metabolism in Liver of Diabetic Rats

目的:探讨红景天苷对糖尿病大鼠肝脏糖脂代谢作用机制。方法:6~7周龄雄性Zucker糖尿病(ZDF)(fa/fa)大鼠24只,按照血糖随机分为模型组,红景天苷低剂量组(0.05g·kg^-1),红景天苷高剂量组(0.1g·kg^-1),8只/组,另选同周龄ZDF(fa/+)大鼠8只为正常组,连续给药干预6周。实验结束后,检测大鼠空腹血糖(fasting blood glucose,FBG),甘油三酯(triglyceride,TG),总胆固醇(total cholesterol,TC),游离脂肪酸(free fatty acids,FFA),超氧化物酶歧化酶(superoxide dismutase,SOD),丙二醛(malondialdehyde,MDA),过氧化氢酶(catalase,CAT),血清胰岛素水平(fast inginsulin,Fins),胰岛素抵抗指数(homeostasis model assessment insulin resistance,HOMA-IR);蛋白免疫印迹法(Westernblot)检测肝脏蛋白激酶样内质网激酶(PKR-like ER kinase,PERK),核转录因子2相关因子2(NF-E2-relatedfactor 2,Nrf2),血红素氧化酶-1(heme oxidase-1,HO-1)蛋白表达。结果:与正常组比较,模型组大鼠FBG,Fins,HOMA-IR,TC,TG,FFA,MDA明显升高(P<0.05,P<0.01);SOD,CAT明显降低(P<0.05,P<0.01);肝脏p-PERK,Nrf2,HO-1蛋白表达明显降低(P<0.05,P<0.01)。与模型组比较,红景天苷高、低剂量组大鼠FBG,Fins,HOMA-IR,TC,TG,FFA,MDA明显降低(P<0.05,P<0.01);SOD,CAT明显升高(P<0.05,P<0.01);肝脏p-PERK,Nrf2,HO-1蛋白表达明显升高(P<0.05,P<0.01)。结论:红景天苷能够改善糖尿病大鼠糖脂水平、胰岛素抵抗,可能是通过上调p-PERK,Nrf2,HO-1蛋白表达,抑制氧化应激实现的。

Objective: To explore the mechanism of salidroside(SAL) in improving glucose and lipid metabolism in liver of diabetic rats. Method: According to blood glucose,24 male ZDF(fa/fa) rats of 6-7 week old were randomly divided into model group,SAL-low group(0. 05 g·kg-1),SAL-high group(0. 1 g·kg-1),8 rats in each group. Another 8 ZDF(fa/+) rats were selected as normal group. All the rats were administered continuously for 6 weeks. After experiment,fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),free fatty acids(FFA),superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),fasting insulin(Fins), and homeostasis model assessment insulin resistance(HOMA-IR) were measured.Western blot was used to detect phosphorylated PKR-like ER kinase(p-PERK),NF-E2-relatedfactor2(Nrf2),heme oxidase-1HO-1 protein expression levels in liver. Result: As compared with normal group,FBG,Fins,HOMA-IR,TC,TG,FFA,and MDA were increased significantly in model group(P < 0. 05,P < 0. 01),while SOD,CAT levels were significantly decreased(P < 0. 05,P < 0. 01);the protein expression levels of p-PERK,Nrf2,and HO-1 in control group were significantly decreased in model group(P < 0. 05,P < 0. 01). As compared with model group, FBG, Fins, HOMA-IR, TC, TG, FFA, and MDA levels were decreased significantly(P < 0. 05,P < 0. 01),while SOD and CAT levels were significantly increased in SAL low and high groups(P < 0. 05,P < 0. 01);and the protein expression levels of p-PERK,Nrf2,and HO-1 in SAL group were significantly increased(P < 0. 05,P < 0. 01). Conclusion: The Salidroside can improve metabolism of glucose and lipid,IR in diabetic rats,and the mechanism may be associated with inhabiting oxidative stress through the upregulation of p-PERK,Nrf2,and HO-1 protein expression.