基于IRS-1/PI3K/Akt信号通路探讨葛根-茯苓发酵产物对T2DM大鼠糖脂代谢的影响  

Effects of Puerariae Lobatae Radix-Poria fermentation products on glycolipid metabolism in T2DM rats based on IRS-1/PI3K/Akt signaling pathway

作　　者：李津 雷晓蕾 闫世琛 刘国 高丽 王永辉 LI Jin;LEI Xiaolei;YAN Shichen;LIU Guo;GAO Li;WANG Yonghui(Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]山西中医药大学,晋中030619

出　　处：《中华中医药杂志》2025年第1期390-395,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81273659);山西省基础研究计划项目(No.202203021221198);山西省重点实验室建设项目(No.zyyyjs2024023);山西省中医药管理局科研课题计划(No.2023ZYYC057);山西中医药大学博士科研启动基金项目(No.2023BK53);山西中医药大学科技创新能力培育计划资助项目(No.2021PY-JC-16)。

摘　　要：目的:基于胰岛素受体底物1(IRS-1)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)通路探讨葛根-茯苓(简称GF)发酵产物对2型糖尿病(T2DM)模型大鼠糖脂代谢的影响。方法:将50只SD大鼠随机分为正常对照组、模型对照组、阳性药对照组、GF未发酵药物组、GF发酵药物组,除正常对照组外,其余组大鼠采用高脂饲料联合链脲佐菌素(STZ)注射方式制备T2DM模型。阳性药物对照组灌胃给予二甲双胍91mg/kg,GF未发酵药物组及GF发酵药物组灌胃给予相应药物水煎液13g/kg,正常对照组及模型对照组给予等体积0.9%氯化钠溶液,持续8周。给药结束后测定空腹血糖(FBG)、餐后2h血糖(2hPBG)、糖化血红蛋白(HbAlc)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹胰岛素(FINS)水平及胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI),苏木素-伊红(HE)染色观察肝脏病理学变化,Western Blot检测大鼠肝脏IRS-1、PI3K、Akt蛋白水平,采用RT-qPCR检测大鼠肝脏IRS-1、PI3K、Akt mRNA表达情况。结果:与正常对照组比较,模型对照组大鼠FBG、2hPBG、HbAlc、TC、TG、LDL-C、FINS、HOMA-IR水平显著升高(P<0.01),HDL-C、ISI水平显著降低(P<0.01);肝脏组织脂肪样变性、炎症浸润明显;肝脏组织中IRS-1、PI3K、Akt蛋白及mRNA水平显著降低(P<0.01)。与模型对照组比较,各给药组FBG、2hPBG、HbAlc、TC、TG、LDL-C、HOMA-IR、FINS水平显著降低(P<0.05,P<0.01),HDL-C水平显著升高(P<0.05,P<0.01),阳性药对照组、GF发酵药物组ISI水平显著升高(P<0.01);各给药组肝脏组织脂肪样变性、炎症浸润减少;各给药组肝脏组织中IRS-1、Akt蛋白和IRS-1、PI3K、AKT mRNA表达量显著升高(P<0.05,P<0.01),阳性药对照组、GF发酵药物组PI3K蛋白表达量显著升高(P<0.05,P<0.01),其中GF发酵药物组较未发酵药物组治疗效果更佳。结论:葛根茯苓发酵产物可改善T2DM大鼠的糖脂代谢,�Objective:To investigated the effects of Puerariae Lobatae Radix-Poria(GF) fermentation products on glycolipid metabolism in type 2 diabetes mellitus(T2DM) model based on IRS-1/PI3K/Akt pathway.Methods:Fifty SD rats were randomly divided into normal control group,model control group,positive drug control group,GF unfermented drug group and GF fermented drug group.The T2DM model was prepared by high fat feed combined with streptozotocin(STZ) injection except normal control group.Positive drug control group was given metformin 91mg/kg by intragastric administration,GF unfermented drug and GF fermentation group were given GF unfermented drug to aqueous decoction 13 g/kg and GF fermentation drug to aqueous decoction 13 g/kg by intragastric administration,normal control group and model control group were given equal volume of normal saline for 8 weeks.The determination of fasting blood glucose(FBG),2h postprandial blood glucose(2hPBG),glycosylated hemoglobin(HbAlc),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),fasting insulin(FINS) level and insulin resistance index(HOMA-IR)(insulin sensitivity index(ISI),liver pathological changes were observed by hematoxylin-eosin(HE) staining.The levels of IRS-1,PI3K,Akt protein were detected by protein immunoblotting(Western Blot).The mRNA expression of IRS-1,PI3K and Akt in rats was measured by quantitative reverse PCR(RT-qPCR).The levels of fasting blood glucose(FBG),2hPBG,HbAlc,total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),fasting insulin(FINS),insulin resistance index(HOMA-IR) and insulin sensitivity index(ISI) were measured after administration.Hematoxylineosin(HE) staining were used to observe the pathological changes of the liver.The levels of IRS-1,PI3K and Akt in the liver of rats were detected by Western Blot.Quantitative reverse transcription PCR(RT-qPCR) was used to detect the mRNA expression of IRS-1,PI3K and A

关 键 词：葛根 茯苓 发酵 糖脂代谢 胰岛素受体底物1 磷脂酰肌醇3-激酶 蛋白激酶 2型糖尿病 

分 类 号：R285.5[医药卫生—中药学]