新诊断2型糖尿病患者血清炎症因子及外周血单个核细胞中核因子κB活性变化

Changes in Serum Inflammation Markers and Nuclear Factor κB Activity in Peripheral Blood Mononuclear Cell from Patients with Newly Diagnosed Type 2 Diabetics

目的探讨新诊断2型糖尿病患者血清炎症因子超敏-C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)水平及外周血单个核细胞(PMNC)中NF-κB的活性变化。方法选择健康成人66例,新诊断2型糖尿病患者92例,分为正常对照组和2型糖尿病组,分析比较两组血清炎症因子及PMNC中NF-κB活性水平。血清hs-CRP、TNF-α、IL-6采用酶联免疫吸附法测定。免疫印迹分析检测PMNC中核因子κBp65(Ser536)的磷酸化水平,β-actin作为内参。结果2型糖尿病组患者的血清CRP、IL-6、TNF-α水平均显著高于正常对照组(P<0.001);糖尿病组患者PMNC中NF-κBP65(Ser536)磷酸化水平高于正常对照组(0.85±0.38vs0.47±0.25,P<0.05);在糖尿病组,log(CRP)与质量指数(BMI)、腰围、腰臀比、稳态模型法估计的胰岛素抵抗指数(HOMA-IR)、log(IL-6)、log(TNF-α)、糖基化血红蛋白(hemoglobin,A1c)呈正相关。结论结果提示2型糖尿病患者处于炎症状态,血清炎症因子水平及PMNC中NF-κB活性的升高可能与胰岛素抵抗和动脉粥样硬化的形成有关。

[Objective] To investigate the changes of serum inflammation markers including high sensitivity Creactive protein （hs-CRP）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and nuclear factor κB （NF-κB） activity in peripheral blood mononuclear cell （PMNC） from the patients with newly diagnosed type 2 diabetic. [ Methods ] Sixty-six normal individuals and 92 newly diagnosed type 2 diabetics were selected. All subjects were divided into two groups： control subjects and type 2 diabetics. Levels of serum inflammation makers and level of NF- κB p65 phosphorylation were compared between control subjects and type 2 diabetics. Serum hs-CRP, TNF-α, and IL-6 were assayed by enzyme linked immunosorbent assay. Phosphorylation status of NF-κB p65 of PMNC was determined by immunoblotting with phosphor-specific antibodies to NF-κB p65 （Ser^536）. [Results] Levels of serum hs-CRP, TNF-α, and IL-6 were higher in diabetic patients than those in control subjects （P〈 0.（301）. The level of NF-κB p65 phosphorylation was increased in newly diagnosed type 2 diabetic patients compared with control subjects（0.85±0.38 vs 0.47±0.25, P〈 0.05）. In the diabetes patients, CRP correlated significantly with body mass index（BMI）, waist circumference（W）, waist-to-hip ratio （WHR）, homeostdsis model assessment-insulin resistance （HOMA-IR）, log（IL-6）, log（TNF-6）, and hemoglobin A1c （GHbA1C）. [Conclusion] Type 2 diabetics had higher level of inflammation factors. The increased activity of NF-κB in PMNC of type 2 diabetic patients may contribute to insulin resistance and atherogenesis.