紫杉叶素调控PI3K/AKT/mTOR通路对糖尿病模型大鼠氧化应激和胰岛功能的机制研究  

Effect of Taxifolin on Oxidative Stress and Pancreatic Islet Function in Diabetes Model Rats by Regulating PI3K/AKT/mTOR Pathway

作　　者：赵超[1] 齐保险 李哲 马云 ZHAO Chao;QI Baoxian;LI Zhe;MA Yun(Jieshou People's Hospital,Jieshou 236500,Anhui,China)

机构地区：[1]界首市人民医院,安徽界首236500

出　　处：《中西医结合心脑血管病杂志》2024年第17期3151-3157,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:探索紫杉叶素(TAX)调控磷脂酰肌醇3-激酶(PI3K)/丝苏氨酸蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路对糖尿病模型大鼠氧化应激和胰岛功能的影响。方法:102只无特定病原体(SPF)级SD大鼠高脂高糖饮食饲养4周,建立2型糖尿病大鼠模型,造模成功后随机分为Model组、TAX低剂量组(5 mg/kg)、TAX中剂量组(10 mg/kg)、TAX高剂量组(20 mg/kg)、PI3K激活剂组(0.02 mg/kg PI3K激活剂740Y-P+20 mg/kg TAX)、mTOR激活剂组(10 mg/kg mTOR激活剂MHY1485+20 mg/kg TAX),每组12只。另外取12只正常大鼠作为Control组,造模成功后,给予相应药物,每日1次,连续干预5周。测量各组大鼠体质量;血糖仪检测空腹血糖(FBG);对各组大鼠进行葡萄糖耐量试验(OGTT);酶联免疫吸附测定法(ELISA)测定大鼠血清空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(ISI);苏木精-伊红(HE)染色观察大鼠胰腺组织损伤情况,计算胰岛个数;全自动生化分析仪检测大鼠血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)水平;试剂盒检测大鼠血清丙二醛(MDA)、活性氧(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;蛋白免疫印迹法(Western Blot)检测大鼠胰腺组织中PI3K/AKT/mTOR通路蛋白表达。结果:与Control组比较,Model组大鼠体质量、FBG、OGTT(0.5、1.0、2.0 h)血糖值、FINS、HOMA-IR、TC、TG、LDL-C、FFA、ROS、MDA、p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR增加,ISI、HOMA-β、HDL-C、GSH-Px、SOD、胰岛数量降低(P<0.05);与Model组比较,TAX低剂量组、TAX中剂量组、TAX高剂量组大鼠体质量、FBG、OGTT(0.5、1.0、2.0 h)血糖值、FINS、HOMA-IR、TC、TG、LDL-C、FFA、ROS、MDA、p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR水平降低,ISI、HOMA-β、HDL-C、GSH-Px、SOD、胰岛数量增加(P<0.05);PI3K、mTOR激活剂均减�Objective:To explore the impacts of taxifolin(TAX)on oxidative stress and pancreatic islet function in diabetes model rats by regulating phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Methods:One hundred and two Sprague-Dawley(SD)rats without specific pathogen(SPF)were randomly divided into Model group,TAX low-dose group(5 mg/kg),TAX medium-dose group(10 mg/kg),TAX high-dose group(20 mg/kg)and,PI3K activator group(0.02 mg/kg PI3K activator 740Y-P+20 mg/kg TAX),mTOR activator group(10 mg/kg mTOR activator MHY1485+20 mg/kg TAX),with 12 rats in each group.In addition,with 12 normal rats were selected as Control group.The body mass of each rat was measured.Fasting blood glucose(FBG),glucose tolerance test(OGTT)and fasting insulin(FINS)were measured.Homeostasis model assessment-IR(HOMA-IR),pancreatic isletβcell function index(HOMA-β)and insulin sensitivity index(ISI)were calculated.Hematoxylin-eosin(HE)staining was used to observe the pancreatic tissue injury of rats,and the number of islets was calculated.The serum levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),and free fatty acid(FFA)were detected.Serum malondialdehyde(MDA),reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels were detected by the kit.Western Blot was used to detect the expression of PI3K/AKT/mTOR pathway protein in rat pancreas.Results:Compared with the Control group,body mass,FBG,OGTT(0.5,1.0,2.0 h)blood glucose,FINS,HOMA-IR,TC,TG,LDL-C,FFA,ROS,MDA,p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR increased in Model group,ISI,HOMA-β,HDL-C,GSH-Px,SOD,islet number decreased(P<0.05).Compared with Model group,body mass,FBG,OGTT(0.5,1.0,2.0 h)blood glucose,FINS,HOMA-IR,TC,TG,LDL-C,FFA,ROS,MDA,p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR levels of rats in TAX low-dose group,TAX medium-dose group and TAX high-dose group decreased,ISI,HOMA-β,HDL-C,GSH-Px,SOD,and islets increased(P<0.05).Both

关 键 词：糖尿病 氧化应激 紫杉叶素 磷脂酰肌醇3-激酶/丝苏氨酸蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路 胰岛功能 实验研究 

分 类 号：R285.5[医药卫生—中药学]