辛开苦降方对初发2型糖尿病KKay小鼠肝脏IRS-2/PI3K通路的影响  

Impacts of Xinkaikujiang Formula on Liver IRS-2/PI3 Pathway in KKay Mice of Early T2DM

作　　者：张艳红[1] 张先慧[1] 胡照娟[1] 张冬梅[1] 娄利霞[1] 柳红芳[1] 

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《世界中西医结合杂志》2013年第11期1099-1102,1106,共5页World Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81072735)

摘　　要：目的研究辛开苦降方对KKay 2型糖尿病(T2DM)小鼠肝脏胰岛素受体底物-2/磷脂酰肌醇3-激酶通路(IRS-2/PI3K)的影响。方法将小鼠随机分为辛开组、苦降组、辛开苦降组、罗格列酮组、模型组。对照组选10周龄雄性C57BL/6J小鼠10只。对照组及模型组给予0.5%羧甲基纤维素钠溶液(CMC)。灌胃给药四周后测血浆葡萄糖(FBG),及胰岛素浓度(FINS),免疫蛋白质印迹法(Western blotting)测定肝组织IRS-2、P-IRS-2(磷酸化胰岛素受体底物-2)、PI3K、PPI3K(磷酸化磷脂酰肌醇3-激酶)、IRS-3、IRS-4蛋白表达水平,RT-PCR法测定肝组织PI3K、IRS-2、IRS-3、InsR(胰岛素受体)的mRNA表达水平。结果与模型组比较,苦降组、马来酸罗格列酮组血糖明显降低(P<0.05)。与模型组比较,各给药组小鼠胰岛素浓度均降低,IAI均升高(P<0.05)。辛开苦降组、辛开组、苦降组可增强T2DM KKay小鼠IRS-2及其磷酸化形式的蛋白表达(P<0.05),抑制负性调节因子IRS-3、4蛋白表达(P<0.05)。辛开苦降组可以增强PI3K、P-PI3K蛋白表达量及PI3-K mRNA表达(P<0.05)。各给药组间相比,各指标差异均无统计学意义(P>0.05)。结论辛开苦降方及其拆方可改善胰岛素抵抗,可能是通过恢复肝脏细胞内正调控和负调控IRS蛋白的平衡实现的。Objective To study the impacts of Xinkaikujiang Formula on IRS -2/PI3K pathway in KKay Mice of type 2 diabetes mellitus （T2DM）. Methods The mice were randomized into a Xinkai Formula group, a Kujiang Formula group, Xinkaikujiang Formula group, a Rosiglitanzone （RSG）group and a model group. Ten male C57BL/6J mice of 10 weeks old were selected in a normal control group. In the normal group and the model group,0.5% CMC was in medication via gastric infusion. Four weeks later, FBG and FINS were detected. Western blotting method was used to determine the protein expressions of IRS - 2, P - IRS - 2,PI3K,P- PI3K,IRS- 3 and IRS -4 in liver tissue. RT -PCR was applied to determine the mRNA ex- pressions of PI3 K, IRS - 2, IRS - 3 and InsR in liver tissue. Results Compared with the model group, FBG was reduced obviously in the Kujiang Formula group and the RSG group （P 〈 0.05 ）. Compared with the mod- el group, FINS was reduced in the mice of each medication group and IAI were all increased （P 〈 0.05 ）. The protein expressions of IRS - 2 and phosphorylated proteins were enhanced in T2DM KKay mice in the Xin- kaikujiang Formula group, the Xinkai Formula group and the Kujiang Formula group（ P 〈 O. 05 ）and the pro- tein expressions of the negative adjustment factors, such as IRS - 3 and 4 were inhibited（ P 〈 0.05 ）. The pro- tein expressions of PI3K and P - P13K as well as mRNA expression of PI3 - K were enhanced in the Xin- kaikujiang Formula group（ P 〈 0.05 ）. The differences in the indexes were not significant in comparison a- mong the medication groups （ P 〉 0.05 ）. Conclusion Xinkaikujiang Formula and its relevant separating for- mulas improve insulin resistance through recovering the balance between the positive control and negative control of IRS proteins in liver cells.

关 键 词：2型糖尿病 辛开苦降方 KKAY小鼠 胰岛素抵抗 IRS-2 PI3K通路 

分 类 号：R285.5[医药卫生—中药学] R587.1[医药卫生—中医学]