沙格列汀对新诊断2型糖尿病患者血清炎症因子及外周血单个核细胞核因子κB活性的影响

Effects of Saxagliptin on Serum Inflammation Markers and Nuclear Factor κB Activity in Peripheral Blood Mononuclear cells in Newly Diagnosed Type 2 Diabetes Patients

目的前瞻性观察沙格列汀治疗对新诊断2型糖尿病(T2DM)患者血清炎症因子及外周血单个核细胞(PMNC)核因子κB(NF-κB)活性的影响。方法 30例新诊断T2DM患者,口服沙格列汀片治疗12周,观察治疗前后空腹血糖、餐后2 h血糖、糖化血红蛋白(HbA1C)、血压、体质量、体质量指数(BMI)、血脂谱、稳态模型评估的胰岛素抵抗指数(HOMA-IR)、血清炎症因子:超敏C反应蛋白(hs-CRP)、白介素-6(IL-6)、肿瘤坏死因子(TNF-α)水平及PMNC核因子κB p65(Ser536)活性。血清炎症因子采用酶联免疫吸附法测定;PMNC NF-κB(Ser536)活性采用western blot检测。结果沙格列汀治疗12周后,空腹血糖、餐后2 h血糖、HbA1c、体质量、BMI、HOMA-IR指数较治疗前明显下降(P<0.05或0.01)。患者收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)较治疗前无明显变化。外周血PMNC磷酸化NF-κB p65(Ser536)水平及血清炎症因子水平均较基线明显降低(P<0.05或0.01)。协方差分析显示治疗12周时血清hs-CRP水平仍显著低于治疗前(F=5.835,P<0.05)。结论沙格列汀有效降低新诊断T2DM患者血糖,并抑制血清炎症因子水平及外周血PMNC NF-κB活性,发挥独立于降糖外的抗炎作用。

Objective To investigate the effects of saxagliptin on serum inflammation markers and nuclear factor KB （NF-KB） activity in peripheral blood mononuclear cells （PMNC） in newly diagnosed type 2 diabetes patients. Methods A total of 30 newly diagnosed type 2 diabetes patients underwent saxagliptin treatment （5 mg QD） for 12 weeks. The change of fasting plasm glucose（FPG）, 2 h postprandial blood glucose（2 hPPG）, HbA1C, blood lipids, SBP, DBP, weight, BMI, homeostasis model assessment for insulin resistance index （HOMA-IR） were evaluated after 12 weeks treatment. Furthermore, serum levels of inflammatory cytokines ： high sensitivity C reactive protein （ hs-CRP）, interleukin-6 （IL-6）, tumor necrosis factor-or （TNF-cL） were assayed by enzyme linked immunosorbent assay, phosphorylation status of NF-KB p65 （Ser536） in PMNC was measured by western blot at the start （0 w） and the endpoint （12 w）. Results Over the 12 weeks treatment period, FPG, 2 hPPG, HbA]c, weight, BMI, and HOMA-IR were significantly decreased （ P 〈 0.05 or 0.01 ）. There were not significant variations of SBP, DBP, TC, TG, LDL-C, HDL-