山药多糖对地塞米松诱导IR-3T3-L1脂肪细胞的降血糖作用及机制研究  

Hypoglycemic effect of Chinese yam polysaccharide on DEX-induced IR-3T3-L1 adipocytes

作　　者：刘昕玥 王凤忠[1] 郑涵文 Alberto Carlos Pires Dias 范蓓[1] 王琼 LIU Xinyue;WANG Fengzhong;ZHENG Hanwen;ALBERTO Carlos Pires Dias;FAN Bei;WANG Qiong(Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences,Risk Assessment Laboratory of Agricultural Products Processing Quality and Safety,Key Laboratory of Agricultural Products Quality and Safety Collection,Storage and Transportation Control,Ministry of Agriculture and Rural Affairs,Beijing 100193,China;Sino-Portugal TCM International Cooperation Center,the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000;Sino-PT Research Center for Medicinal and Food Plant Resources,Department of Biology,University of Minho,Braga 4710-057,Portugal)

机构地区：[1]中国农业科学院农产品加工研究所/农业农村部农产品加工质量安全风险评估实验室/农业农村部农产品质量安全收贮运管控重点实验室,北京100193 [2]西南医科大学附属中医医院中葡中医药国际合作中心,四川泸州646000 [3]葡萄牙米尼奥大学生物系中葡药食植物资源研究中心,葡萄牙布拉加4710-057

出　　处：《中国比较医学杂志》2024年第4期73-83,共11页Chinese Journal of Comparative Medicine

基　　金：国家重点研发计划(2021YFD1600100);高端外国专家引进计划(G2022051012L)。

摘　　要：目的探究山药多糖(Chinese yam polysaccharide,CYPS)在地塞米松(dexamethasone,DEX)诱导的3T3-L1胰岛素抵抗(IR-3T3-L1)细胞模型中的降血糖作用。方法将IR-3T3-L1脂肪细胞随机分为对照组(Con)、DEX组(DEX)、Met组(Met,阳性药组)、CYPS组(0.05、0.15、0.45 mg/mL),通过DEX(1μmol/L)诱导建立IR-3T3-L1细胞模型,进行给药后细胞对葡萄糖的消耗量和细胞中血脂(总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C))与丙二醛(malondialdehyde,MDA)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、己糖激酶(hexokinase,HK)、丙酮酸激酶(pyruvate kinase,PK)含量的检测,并采用qRT-PCR对AMPK-PI3K/Akt信号通路中相关基因表达进行检测。结果DEX组与Con组相比,1μmol/L DEX处理48 h显著降低了IR-3T3-L1细胞的葡萄糖消耗量(P<0.01),且在60 h内维持稳定。0.05、0.15、0.45 mg/mL CYPS处理IR-3T3-L1细胞显著增加了细胞中葡萄糖的消耗(P<0.01)、HK、PK、GSH-Px酶活性(P<0.01)、HDL-C含量(P<0.01);降低了MDA酶活性(P<0.01)、T-CHO、TG、LDL-C含量(P<0.01)。同时,CYPS可以显著回调PI3K、Akt、GLUT-4、AMPK、IRS-2、PPARa、Adiponectin的mRNA水平(P<0.05),降低IRS-1、GSK-3β、ACC、FAS的mRNA表达水平(P<0.01)。结论CYPS能够改善DEX诱导的IR-3T3-L1细胞对葡萄糖的消耗,调节脂代谢紊乱,缓解氧化应激,其作用机制可能通过调控IR-3T3-L1脂肪细胞的AMPK-PI3K/Akt信号通路来实现糖脂代谢紊乱和胰岛素抵抗调节来实现。Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on the 3T3-L1 insulin resistance cell model.Methods IR-3T3-L1 adipocytes were randomly divided into control group(Con),model group(DEX),metformin group(Met,positive drug group)and CYPS group(0.05,0.15,0.45 mg/mL).After the creation of the IR-3T3-L1 cell model by dexamethasone(DEX)(1μmol/L)stimulation,Chinese yam polysaccharide treatment was applied.Glucose intake and the levels of TC,TG,LDL-C,HDL-C,GSH-Px,MDA,HK,and PK were then measured.AMPK-PI3K/Akt signaling pathway-associated gene expression was identified using qRT-PCR.Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1μmol/L DEX compared to that of the Con group(P<0.01),and the reduction persisted for 60 hours.0.05,0.15,0.45 mg/mL CYPS treatment significantly increased glucose consumption(P<0.01),HK,PK,GSH-Px enzyme activities(P<0.01),HDL-C content(P<0.01),and decreased MDA enzyme activity(P<0.01),T-CHO,TG,LDL-C content(P<0.01)in IR-3T3-L1 cells.(P<0.01).Additionally,CYPS administration dramatically decreased PI3K,Akt,GLUT-4,AMPK,IRS-2,PPARa,and adiponectin mRNA expression levels(P<0.05)and reduced IRS-1,GSK-3β,ACC,and FAS mRNA expression levels(P<0.01).Conclusions In IR-3T3-L1 cells,CYPS can reduce oxidative stress,control lipid metabolism disorders,and enhance DEX-induced glucose intake.AMPK-PI3K/Akt signaling pathway-associated genes may be connected to the process.

关 键 词：山药多糖 胰岛素抵抗 地塞米松 3T3-L1细胞 二甲双胍 AMPK-PI3K/Akt信号通路 

分 类 号：R-33[医药卫生]