果蝇样受体4介导游离脂肪酸诱导2型糖尿病大血管病变的研究

The role of TLR4 in free fatty acid induced macrovascular injury in type 2 diabetic patient

目的：通过检测2型糖尿病（T2DM）患者外周血果蝇样受体4（TLR4）的表达和血清游离脂肪酸（FFA）水平，探讨TLR4信号在FFA诱导T2DM大血管病变中的作用。方法选取甘肃省人民医院内分泌科2014年3--6月的T2DM住院患者66例，根据颈动脉内膜中层厚度（IMT）不同分为T2DM无大血管病变组（IMT〈0.9mm）32例及T2DM合并大血管病变组（IMT≥0.9mm）34例。性别、年龄匹配的健康志愿者40例作为对照组。空腹静脉采血检测空腹血糖（FBG）、血脂、胰岛素和糖化血红蛋白等生化指标，比色法测定血清游离脂肪酸（FFA）水平，流式细胞术检测外周血单个核细胞（PBMCs）TLR4表达水平。结果 T2DM合并大血管病变组TLR4表达水平（19.8±3.9）显著高于T2DM无大血管病变组（15.0±3.9）和健康对照组（12.8±2.6）（均P〈0.05）；T2DM合并大血管病变组血清FFA水平（0.520±0.164）mmol/L较正常对照组（0.349±0.212） mmol/L显著增高（均P〈0.05）。 Pearson相关分析提示TLR4与IMT（r=0.545，P〈0.001）、FFA（r=0.266，P〈0.05）与FBG（r=0.445， P〈0.05）均呈正相关，IMT也与FFA（r=0.295，P〈0.05）和FBG（r=0.490，P〈0.05）呈正相关。多元线性回归分析显示：TLR4、FBG、年龄是影响IMT的独立相关因素。结论 TLR4炎症信号通路参与了游离脂肪酸诱导的T2DM大血管病变。

Objective To investigate the role of TLR4 in free fatty acid induced macrovascular injury in patient with type 2 diabetes mellitus （T2DM）. Methods A total of 66 patients with T2DM were classified into two groups based on the value of carotid intima-media thickness（IMT）,32 T2DM patients without macrovascular injury （IMT〈0.9mm） and 34 T2DM pa-tients with macrovascular injury （IMT≥0.9mm） , 40 gender and age matched healthy volunteers were used as control group. Measured fasting blood glucose, lipids, insulin, glycosylated hemoglobin A1, and free fatty acid （FFA）. Flow cytometry （FCM） was used to detect TLR4 protein expression in peripheral blood monocyte cells PBMCs. Results The level of TLR4 in T2DM with macrovascular injury was markedly higher than that in T2DM without macrovascular injury , and the TLR4 expression level in both group were significantly increased compared with that in the control group （all P〈0.05）. The serum level of FFA were markedly elevated in both diabetic group compared with the control group （all P〈0.05）. Moreover, TLR4 was positively corre-lated with IMT（r=0.545）, FFA（r=0.266） and FBG（r=0.445,All P〈0.05）. IMT was also correlated with FFA（r=0.295） and FBG （r=0.490,All P〈0.05）. Multivariate linear stepwise regression analysis showed that TLR4, FBG and age were the independent risk factors for IMT in patients with type 2 diabetes. Conclusion TLR4 signaling pathway involved in the pathogenesis of macrovascular injury induced by FFA in T2DM.