基于IRS-1/PI3K/AKT通路探讨枳葛口服液对酒精性肝病大鼠胰岛素抵抗的影响

To Explore the Effects of Zhige Oral Solution on Insulin Resistance in Rats with Alcoholic Liver Disease Based on IRS-1/PI3K/AKT Pathway

目的探讨枳葛口服液对酒精性肝病大鼠胰岛素抵抗的影响及可能机制。方法SD雄性大鼠100只随机分为5组,正常组(蒸馏水)、模型组(52%老白干)、枳葛口服液高、中、低剂量组(52%老白干+不同剂量枳葛口服液)灌胃。各组大鼠每四周取尾静脉血测定FBG、FINS,持续16周后处死大鼠,取肝组织行HE染色、免疫组化,取肝脏总蛋白Western blotting检测IRS-1、PI3K、AKT、GLUT-2等IRS-1/PI3K/AKT通路相关蛋白表达水平。结果与正常组比较,模型组FBG、FINS明显升高(P<0.05),IRS-1/PI3K/AKT通路相关蛋白水平均显著降低(P<0.01),HE染色及免疫组化可见细胞内较多的脂肪空泡;与模型组比较,枳葛口服液高、中剂量组以上指标均有所改善(P<0.05),低剂量组以上指标无明显改善(P>0.05)。结论乙醇诱导的酒精性肝损伤大鼠存在着胰岛素抵抗及IRS-1/PI3K/AKT通路的改变,一定剂量的枳葛口服液可能通过IRS-1/PI3K/AKT信号通路改善胰岛素抵抗状态。

Objective To investigate the effect and possible mechanism of Zhige Oral Solution on insulin resistance in rats with alcoholic liver disease.Methods 100 SD male rats were randomly divided into five groups:the normal group(distilled water),the model group(52%of Laobaigan),and the high,medium and low dose groups(52%of Laobaigan+different doses of Zhige Oral Solution),with gavage administration.Tail venous blood of each group was taken every four weeks to measure insulin resistance indicators such as FBG,FINS,etc.After 16 weeks,the rats were sacrificed,liver tissues were taken for HE staining and immunohistochemistry,and total liver proteins,such as IRS-1,PI3K,P-PI3K,AKT,P-Akt,and Glut-2,were taken for detection of expression level of IRS-1/PI3K/AKT pathway related proteins.Results The results showed that FBG and FINS in the model group were significantly increased(P<0.05),the expression levels of IRS-1/PI3K/AKT pathway related proteins were significantly decreased(P<0.01),and HE staining and immunohistochemistry showed more fat vacuoles in the cells compared with the normal group.All the tested indicators above showed varying degrees of reversal in the high and medium dose groups(P<0.05)compared with that of the model group.No significant improvement was observed in the low dose group compared with the model group(P>0.05).Conclusion There are changes in insulin resistance and IRS-1/PI3K/AKT pathway in ethanol-induced alcoholic liver injury in rats,and a certain dose of Zhige Oral Solution may improve insulin resistance through IRS-1/PI3K/AKT signaling pathway.