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宋苗苗 雷珂 董增义 陈志红.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[J].现代生物医学进展英文版,2016,16(14):2631-2636.
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 InsulinResistance in Small for Gestational Age Rats
  
DOI:
中文关键词: Toll样受体4  小于胎龄儿  追赶生长  胰岛素抵抗
英文关键词: Toll-like receptor 4  Small for gestational age  Catch-up growth  Insulin resistance
基金项目: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)
Author NameAffiliation
宋苗苗 雷珂 董增义 陈志红 青岛大学附属医院神经内分泌儿科青岛大学附属医院儿科研究所 
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中文摘要:
      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-alpha;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kB、肿瘤坏死因子-alpha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、核因子资B、肿瘤坏死因子-琢和白介素-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-alpha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。
英文摘要:
      Objective:To investigate the effect of the toll-like receptor4 (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 S1: 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-alpha(TNF-alpha)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-alpha 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-琢and IL-6in group S1 gradually became higher than that of in group AGA and group S2 (P<0.05). The mRNA expression level of TLR-4, MyD88, NF-kB, TNF-alphaand 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 groupS1, 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).Conclusion:Abnormal glucose and lipid metabolismhappened 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-alpha and IL-6, which resulted in chronic inflammatory reaction and promoted the development of insulin resistance. During the progression of the insulin resistance, the adipose tissue play more important role.
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