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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 detect the expression of TLR4 and the level of serum free fatty acid (FFA) in patients with type 2 diabetes mellitus (T2DM) and explore the role of TLR4 in FFA-induced T2DM. Methods Sixty-six patients with T2DM admitted to Department of Endocrinology of People’s Hospital of Gansu Province from March to June 2014 were divided into two groups according to carotid intima-media thickness (IMT): 32 patients with T2DM without macrovascular disease (IMT <0.9mm) and T2DM 34 cases were complicated with macrovascular disease (IMT≥0.9mm). Forty healthy volunteers with gender and age matched as control group. Fasting blood samples were collected for determination of fasting blood glucose (FBG), lipids, insulin and glycosylated hemoglobin biochemical indicators, serum free fatty acid (FFA) levels by colorimetric assay, and peripheral blood mononuclear cells (PBMCs) TLR4 expression levels by flow cytometry. Results The level of TLR4 expression in T2DM complicated with macroangiopathy was significantly higher than that in T2DM without macroangiopathy (15.0 ± 3.9) and healthy controls (12.8 ± 2.6) (all P <0.05). T2DM with macrovascular complications Serum FFA level (0.520 ± 0.164) mmol / L was significantly higher than that of normal control group (0.349 ± 0.212) mmol / L (all P <0.05). Pearson correlation analysis showed that there was a positive correlation between TLR4 and IMT (r = 0.545, P <0.001), FFA (r = 0.266, P <0.05) and FBG , P <0.05) and FBG (r = 0.490, P <0.05). Multivariate linear regression analysis showed that: TLR4, FBG, age were independent factors affecting IMT. Conclusion The TLR4 inflammatory signaling pathway is involved in the free fatty acid-induced T2DM macroangiopathy.