TLR4信号通路及炎症因子对肥胖儿童胰岛素抵抗的影响研究

Effects of TLR4 signaling pathway and inflammatory factors on insulin resistance in obese children

目的研究模式识别受体TLR4信号通路及炎症因子对肥胖儿童胰岛素抵抗的作用及影响。方法以新疆乌鲁木齐市周边地区4所哈萨克族小学7~13岁超重肥胖学龄儿童60名为观察组,年龄、身高、性别匹配的60例正常体质量儿童为对照组,进行体格指标测定,全自动生化分析仪测定空腹血糖(FPG),放免法检测空腹胰岛素浓度(FIN),荧光定量PCR试验测定Toll样受体4(TLR4)、趋化因子CXCL2、髓样分化因子88(MyD88)、肿瘤坏死因子受体相关因子6(TRAF6)、p干扰素TIR结构域衔接蛋白(TRIF)、TRAM炎症因子水平。结果观察组的一般体格测量指标(体质量、体质量指数/BMI,腰围身高比/WHtR),生化指标(胰岛素、空腹血糖、胰岛素抵抗指数/HOMA-IR)均明显高于对照组(P V0.05)。TLR4、MyD88、TRAM、CXCL2、GAPD H的基因相对表达量在观察组水平均明显升高(P V0.05);TLR4G=0.512)、MyD88(r=0.674)、TRAM 0=0.558)与BMI呈正相关,与HOMR-IR、FIN无相关性。结洽肥胖儿童TLR4及其下游MyD88、TRAM信号被激活,目前无证据支持其对胰岛素抵抗发挥直接作用。

Objective To investigate the effects of pattern recognition receptor TLR4 signaling pathway and inflammatory factors on insulin resistance in obese children・Methods 60 overweight and obese school-age children aged 7 to 13 from kazak nationality in the surrounding area of Urumqi in Xinjiang were enrolled asthe observation group, and 60 normal body mass children with age, height and gender were matched as thecontrol group. Body weight, height, body mass index, waist-to-height ratio (WHtR) were measured orcalculated. Fasting plasma glucose (FPG) tested by automatic biochemical analyzer, fasting insulin levels(FIN) tested by radioimmanoassay, TLR4, CXCL2, MyD88, TRAF6, TRIF, TRAM inflammatoryfactor levels were tested by fluorescence quantitative PCR・ Results Baseline is comparable in both groups.General physical measurements (body w&ght, BMI, WHtR), biochemical indicators (insulin, fasting glucose,HOMA-IR) were significantly higher in case group than that of control group (P V0.05). Relativegene expression levels of TLR4, MyD88, TRAM, CXCL2 and GAPDH were significantly increased in the casegroup (P <0.05). TLR4 (r =0.512) , MyD88 (r =0.674) and TRAM (r =0.558) were correlated with BMI, butnot with HOMR-IR and FIN. Conclusion TLR4 and its downstream MyD88 and TRAM signal pathway are activatedin obese Kazakh children, and there is correlation between TLR4 signal pathway and IR.