炎症应激加重CD36基因敲除小鼠胰岛素抵抗  

Inflammatory stress induces insulin resistance in CD36 knockout mice

作　　者：陈显[1] 柳青[1] 雷寒[2] 刘宏[1] 

机构地区：[1]重庆医科大学附属第一医院临床研究中心,重庆400016 [2]重庆医科大学附属第一医院心血管内科,重庆400016

出　　处：《第三军医大学学报》2010年第9期883-886,共4页Journal of Third Military Medical University

基　　金：国家重点基础研究发展计划前期研究专项(973计划;2008CB517309);国家自然科学基金(30670869)~~

摘　　要：目的研究炎症能否加重CD36基因敲除小鼠胰岛素抵抗。方法14周正常饮食喂养的野生型C57BL/6(n=7)和CD36基因敲除(CD36KO)小鼠(n=12),并将CD36KO小鼠按随机数字表法分为炎症刺激组和无炎症刺激组,分别进行糖耐量、胰岛素测定和甘油三酯(TG)、血清淀粉样蛋白A(SAA)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)以及肝脏组织中哺乳动物雷帕霉素靶蛋白(mTOR)、核糖体蛋白S6激酶(S6K)、胰岛素受体底物1(IRS-1)、pIRS-1,2的基因和蛋白表达相关检测。结果与野生型小鼠相比,CD36KO无炎症刺激组存在胰岛素抵抗,胰岛素抵抗指数增加[(3.01±1.24)vs(0.81±0.12),P<0.05],TG增高[(0.83±0.15)mmol/Lvs(0.21±0.06)mmol/L,P<0.05],肝脏mTOR、S6K基因及蛋白水平增高,IRS-1基因及蛋白水平降低,pIRS-1,2蛋白水平增加。与CD36KO无炎症刺激组相比,炎症刺激组小鼠胰岛素抵抗加强,胰岛素抵抗指数增加[(4.65±1.54)vs(3.01±1.24),P<0.05],TG[(2.66±0.17)mmol/Lvs(0.83±0.15)mmol/L,P<0.05],SAA、IL-6、TNF-α水平增高[(13.62±5.05)ng/mlvs(5.74±1.54)ng/ml,P<0.05;(43.81±1.23)pg/mlvs(35.24±4.13)pg/ml,P<0.05;(235.1±32.6)pg/mlvs(169.2±36.1)pg/ml,P<0.05],肝脏的mTOR和S6K基因及蛋白水平增高,IRS-1基因及蛋白水平降低,pIRS-1,2蛋白水平增加。结论炎症应激可以加重CD36基因敲除小鼠胰岛素抵抗。Objective To explore whether the inflammatory stress can increase insulin resistance in the CD36 knockout （KO） mice.Methods After the mice were fed a standard chow for 14 weeks,oral glucose tolerance test,insulin release tests,lipids metabolism,SAA,IL-6,TNF-α and hepatic mRNA and proteins expression of mTOR,S6K,IRS-1,pIRS-1,2 were measured.Results Compared with the wide-type,the CD36 KO mice un-inflamed exhibited insulin resistance,and the insulin resistance index was increased[（3.01±1.24） vs （0.81±0.12）,P0.05],the triglyceride level [（0.83±0.15） mmol/L vs （0.21±0.06） mmol/L,P0.05] together with the hepatic mRNA and protein expression of mTOR and S6K were increased while the IRS-1 expression were reduced,and the protein of pIRS-1,2 were raised.Compared with the CD36 KO un-inflamed control,the inflammatory group represented the elevated lever of insulin resistance[（4.65±1.54）vs（3.01±1.24）,P0.05],triglyceride[（2.66±0.17） mmol/L vs（0.83±0.15）mmol/L,P0.05],SAA[（13.62±5.05） ng/ml vs（5.74±1.54）ng/ml,P0.05],IL-6[（43.81±1.23） pg/ml vs（35.24±4.13）pg/ml,P0.05],TNF-α[（235.1±32.6） pg/ml vs（169.2±36.1）pg/ml,P0.05],at the same time,the hepatic mRNA and proteins expression of mTOR and S6K were increased,while the hepatic mRNA and proteins expression of IRS-1 were reduced,also the protein of pIRS-1,2 were raised.Conclusion The inflammatory stress indeed increases insulin resistance in the CD36 knockout mice.

关 键 词：抗原 CD36 小鼠 基因敲除 炎症 胰岛素抵抗 

分 类 号：R-332[医药卫生] R363.27