姜黄素中枢给药对胰岛素抵抗小鼠的改善作用及其机制研究

Improvement of Curcumin Central Administration on Insulin Resistance Mice and Its Mechanisms

目的观察姜黄素中枢给药对模型小鼠胰岛素抵抗的改善作用,探讨其可能的作用机理。方法将24只C57BL/6J雄性小鼠随机分成低脂组(LF组,n=8)和高脂组(n=16);高脂组高脂饲料喂养12周后形成胰岛素抵抗模型,将其随机分为高脂模型组(HF组,n=8)和姜黄素组(Cur组,n=8)。LF组和HF组侧脑室注射生理盐水4μL,Cur组侧脑室注射40 mmol/L姜黄素4μL,连续给药3 d后,检测葡萄糖耐量以及采用Western Blot法检测肝组织中PEPCK、G6Pase蛋白表达量情况和PKB、S6蛋白磷酸化水平。结果 3组给药后Cur组小鼠的葡萄糖耐量明显低于HF组(P<0.05);Cur组小鼠PKB和S6蛋白磷酸化水平显著高于HF组(P<0.05);Cur组小鼠PEPCK和G6Pase的表达量明显低于HF组(P<0.05)。结论姜黄素中枢给药可明显改善模型小鼠的胰岛素抵抗,其作用可能与增强肝脏胰岛素信号通路相关因子PKB、S6蛋白磷酸化水平和抑制肝脏糖异生有关。

Objective:To observe the effect of curcumin central administration on insulin resistance mouse model by high-fat feeding,and to explore its possible mechanism.Methods:Twenty-four C57 BL/6 male mice were randomly divided into low fat feeding group(LF group,n=8)and high fat feeding group(n=16).The insulin resistance model was formed after high-fat diet for 12 weeks,and randomly divided into a high-fat diet group(HF group,n=8)and curcumin group(Cur group,n=8).The glucose tolerance was measured after continuous administration of the lateral ventricle for 3 days,and the expression of PEPCK,G6 Pase protein and phosphorylation of PKB,S6 protein in liver tissue were detected by Western Blot.Results:The glucose tolerance and the expressions of PEPCK and G6 Pase of Cur group mice was significantly decreased after curcumin central administration compared with HF group(P<0.05),and the phosphorylation levels of PKB and S6 protein in Cur group mice were significantly increased(P<0.05).Conclusion:The central administration of curcumin can significantly improve insulin resistance in model mice,which may be related to the enhancement of phosphorylation of PKB and S6 proteins and the inhibition of hepatic gluconeogenesis in liver insulin signaling pathway.