NOD受体在大鼠骨骼肌胰岛素抵抗中作用

Role of NOD receptor in insulin resistance of rat skeletal muscle

目的探讨核苷酸结合寡聚化结构域(NOD)受体在高脂膳食诱导的不同肥胖易感大鼠骨骼肌胰岛素抵抗中的作用。方法将雄性SD大鼠随机分为对照组和高脂组,分别喂以基础饲料和高脂饲料,8周后高脂组筛选出肥胖易感组和肥胖抵抗组,继续喂养至19周进行口服葡萄糖耐量试验(OGTT),20周后处死大鼠,比较Lee's指数、脂/体比和胰岛素抵抗指数(HOMA-IR),实时荧光定量PCR检测骨骼肌葡萄糖转运体4(GLUT4)、NOD1和NOD2 mRNA表达水平。结果与对照组和肥胖抵抗组比较,肥胖易感组大鼠体重[(770.1±45.9)g]、脂/体比[(7.1±0.6)%]、空腹胰岛素水平[(74.76±6.49)μIU/mL]、HOMA-IR(3.03±0.10)均明显升高(P<0.01);与对照组比较,肥胖抵抗组大鼠体重无明显变化,Lee's指数(313.9±7.3)、脂/体比[(5.6±0.8)%]和HOMA-IR(1.77±0.11)明显升高(P均<0.05);与对照组和肥胖抵抗组比较,肥胖易感组大鼠骨骼肌组织GLUT4mRNA(0.66±0.09)表达下调(P均<0.05),NOD2 mRNA(1.27±0.07)表达上调(P<0.05)。结论高脂膳食可能通过激活大鼠骨骼肌NOD2表达参与该组织胰岛素抵抗。

Objective To investigate the role of nucleotide binding oligomerization domain（NOD）receptor in insulin resistance of skeletal muscle in different obesity susceptible rats induced by high fat diet.Methods Male Sprague-Dawley（SD）rats were randomly divided into control group and high fat group fed with normal and high-fat diet,respectively.The rats in high fat group were subdivided into obesity-prone（OP）group and obesity-resistant（OR）group at 8th week.Oral glucose tolerance test（OGTT）was performed at 19th week and all the rats were sacrificed at 20th week.Lee＇s index,fat content and homeostasis model assessment of insulin resistance（HOMA-IR）were measured.Glucose transporter 4（GLUT4）,NOD1 and NOD2 mRNA expression were determined with real-time PCR.Results Body weight,fat content,fasting insulin level and HOMA-IR in rats of OP group were higher than control and OR group（P〈0.01）.Though there was no difference in body weight between rats in OR and control group,OR group showed higher Lee＇s index,fat content and HOMA-IR compared with those of the control group（P〈0.01 or P〈0.05）.Expression of GLUT4 mRNA in rat skeletal muscle of OP group was down-regulated and NOD2 mRNA was significantly up-regulated than those of the control and OR group（P〈0.01 or P〈0.05）.Conclusion High fat diet might be a NOD2 activator in rat skeletal muscle and play an important role in skeletal muscle insulin resistance.