摘要
目的:探讨石榴花水提物(pomegranate flower water extract,PFW)对 2型糖尿病小鼠肝脏胰岛素信号传导的影响及机制.方法:将C57BL/6J随机分为正常组、模型组、二甲双胍组(Met)、石榴花水提物低剂量组(PFWL)和石榴花水提物高剂量组(PFWH).连续给药 11周后,称小鼠体质量,检测空腹血糖(FBG)、胰岛素(INS)、甘油三酯(TG)和总胆固醇(TC)的含量,计算胰岛素抵抗指数(HOMA-IR);苏木素-伊红(HE)染色观察肝组织病理变化;Western blot法检测肝组织中胰岛素受体底物 1(IRS1)、p-IRS1(Ser307)、蛋白激酶B(AKT)、p-AKT(Ser473)、糖原合成酶激酶-3β(Gsk3β)、p-Gsk3β(S9)、芳香烃受体(AhR)、磷脂酰乙醇胺N-甲基转移酶(PEMT)、Bcl-2/腺病毒E1B-19kDa相互作用蛋白 3(BNIP3)蛋白表达.结果:与模型组比较,PFWH组FBG、INS、HOMA-IR、TG和TC含量极显著降低(P＜0.01);PFWH组小鼠肝细胞内脂肪滴明显减少;PFWH组极显著升高肝脏中IRS1、p-AKT(Ser473)/AKT、p-Gsk3β(S9)/Gsk3β、BNIP3蛋白表达(P＜0.01),极显著降低p-IRS1(Ser307)/IRS1、AHR、PEMT蛋白表达(P＜0.01).结论:PFW可能通过调节AHR/BNIP3抑制肝脏脂质沉积,改善p-IRS1(Ser307)/p-AKT(Ser473)/p-GSK3β(S9)胰岛素信号通路转导.
Abstract
Objective:To investigate the effects and mechanisms of pomegranate flower water extract on hepatic insulin signaling in type 2 diabetic mice.Methods:C57BL/6J was randomly divided into normal group,model group,metformin group(Met),pomegranate flower water extract low-dose group(PFWL)and pomegranate flower water extract high-dose group(PFWH).The drug was administered continuously for 11 weeks.Mice were tested for body mass,fasting blood glucose(FBG),insulin(INS),triglycerides(TG),total cholesterol(TC)and insulin resistance index(HOMA-IR)was calculated.Hematoxylin-eosin(HE)staining was used to observe the pathologic changes in hepatic tissue.The expression levels of insulin receptor substrate 1(IRS1),p-IRS1(Ser307),protein kinase B(AKT),p-AKT(Ser473),glycogen synthase kinase-3β(Gsk3β),p-Gsk3β(S9),aromatidic hydrocarbon receptor(AhR),phosphatidylethanolamine N-methyltransferase(PEMT),and Bcl-2/adenovirus E1B19-kDa interacting protein 3(BNIP3)in mouse liver tissues were determined by Western blot.Results:Compared with the model group,the FBG,INS,HOMA-IR,TG and TC levels were significantly decreased in the PFWH group(P＜0.01).Intracellular fat droplets were significantly decreased in the liver of mice in the PFWH group.Western blot results showed that compared with the model group,IRS1,p-AKT(Ser473)/AKT,p-Gsk3β(S9)/Gsk3β,and BNIP3 protein expression were significantly increased in the liver of the PFWH group(P＜0.01),and p-IRS1(Ser307)/IRS1,AHR,and PEMT protein expression were significantly decreased(P＜0.01).Conclusion:PFW may inhibit hepatic lipid deposition by modulating AHR/BNIP3,and improve p-IRS1(Ser307)/p-AKT(Ser473)/p-GSK3β(S9)insulin signaling pathway transduction.
基金项目
新疆天然药物活性组分与释药技术重点实验室(XJDX1713)
国家自然科学基金项目(81760767)
新疆医科大学博士启动基金(2019-017)
国家科技期刊平台
NSTL
万方数据