Toll样受体4在小于胎龄儿生后发生胰岛素抵抗的作用研究  

The Effect of the Tool-like Receptor 4 Signaling Pathway on Insulin Resistance in Small for Gestational Age Rats

作　　者：宋苗苗[1] 雷珂[2] 董增义[2] 陈志红[1] 

机构地区：[1]青岛大学附属医院神经内分泌儿科,山东青岛266003 [2]青岛大学附属医院儿科研究所,山东青岛266003

出　　处：《现代生物医学进展》2016年第14期2631-2636,共6页Progress in Modern Biomedicine

基　　金：青岛市科技计划项目(13-1-3-28-nsh);国家自然科学基金项目(81170762)

摘　　要：目的:探讨Toll样受体4在小于胎龄儿生后发生胰岛素抵抗的作用。方法:建立动物模型,分为小于胎龄儿追赶生长组(S1组)、小于胎龄儿无追赶生长组(S2组)、适于胎龄儿组(AGA组)。生后4周和12周取血、肝脏和脂肪组织,检测血糖、胰岛素、甘油三酯、游离脂肪酸和总胆固醇,计算胰岛素抵抗指数(Homeostasis model assessment for insulin resistance index,HOMA-IR);ELISA法检测血清白介素-6、肿瘤坏死因子-α;实时定量RT-PCR法检测相同体质量肝脏和脂肪组织中Toll样受体4、髓细胞样分化因子88、核因子κB、肿瘤坏死因子-α和白介素-6 mRNA的表达。结果:与适于胎龄儿组和小于胎龄儿无追赶生长组相比,小于胎龄儿追赶生长组随年龄增长血糖、血清胰岛素、游离脂肪酸、甘油三酯和HOMA-IR逐渐增高(P<0.05),相同体质量肝脏和脂肪组织中Toll样受体4、髓细胞样分化因子88、核因子κB、肿瘤坏死因子-α和白介素-6 mRNA表达量也逐渐升高(P<0.05);肝脏和脂肪组织中Toll样受体4信号通路与胰岛素抵抗指数HOMA-IR呈显著正相关(P<0.05),脂肪组织中的相关性显著高于肝脏组织(P<0.05)。结论:SGA生后追赶生长者随年龄增长出现糖脂代谢异常;肝脏和脂肪组织Toll样受体4信号途径激活,诱发以TNF-α和IL-6为炎性介质的慢性炎症,促进胰岛素抵抗发生发展;脂肪组织在胰岛素抵抗发生发展中作用更强。Objective： To investigate the effect of the toll-like receptor 4 （TLR-4） signaling pathway on insulin resistance in small for gestational age （SGA） rats after birth. Methods： Establishment of the SGA rat model was made by the starvation method in pregnant rats. Experiment group were divided into three groups： （1）Group SI： SGA with catch-up growth; （2）Group S2： SGA without catch-up growth; （3）Group AGA： Appropriate for gestational age （AGA）. Blood, liver and omental adipose tissue were collected on the 4th and 12th week after birth. The serum level of tumor necrosis factor-α （TNF-α）and interleukin-6 （IL-6）were detected by ELISA method. The concentration of fasting blood-glucose, fasting insulin, free fatty acids, triglyceride, total cholesterol were analyzed. Homeostasis model assessment for insulin resistance index （HOMA-IR） was calculated. The mRNA expression of TLR-4, myeloid differentiation factor 88 （MyD88）, nuclear factor KB （NF-KB）, TNF-α and IL-6 in liver and omental adipose tissue were evaluated by real-time quantitative RT-PCR. Results： Along with the growth, the serum level of fasting blood-glucose, fasting insulin, free fatty acids, triglyceride, total cholesterol, TNF-α and IL-6in group S1 gradually became higher than that of in group AGA and group S2 （P 〈0.05）. The mRNA expression level ofTLR-4, MyD88, NF-KB, TNF-α and IL-6 in liver and omental adipose tissue in group S1 were remarkably higher than that of in group AGA and groupS2 （P〈0.05）. In groupSl, the TLR-4 signaling pathway was positively related to HOMA-IR. Higher degree of correlation was observed in omental adipose tissue than in liver （P 〈0.05）. Conclusions： Abnormal glucose and lipid metabolism happened in SGA rats with catch-up growth with advancing age. Activation of TLR-4 signaling pathway in liver and adipose tissue induced the releasement of inflammatory cytokines such as TNF-α and IL-6, which resulted in chronic inflammatory reaction and promoted the

关 键 词：TOLL样受体4 小于胎龄儿 追赶生长 胰岛素抵抗 

分 类 号：Q95-3[生物学—动物学] R725.8[医药卫生—儿科]