新诊断2型糖尿病患者二甲双胍治疗后外周血单个核细胞核因子κB活性的变化  

Peripheral blood mononuclear cell nuclear factor kappa B activity following metformin treatment in newly diagnosed type 2 diabetics patients

作　　者：石秀林[1] 李焱[2] 严励[2] 黎峰[2] 徐明彤[2] 刘丹[2] 程桦[2] 

机构地区：[1]福建医科大学附属厦门第一医院内分泌科,厦门市糖尿病研究所,福建省厦门市361003 [2]中山大学附属第二医院内分泌科,广东省广州市510120

出　　处：《中国组织工程研究与临床康复》2009年第6期1135-1138,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：福建省卫生厅青年科研课题(2007-2-49)~~

摘　　要：背景:IKK/核因子κB通路是巨噬细胞分泌炎症因子的关键调节通路,可启动、放大炎症反应,二甲双胍可能有潜在的抗炎作用。目的:探讨二甲双胍对新诊断2型糖尿病患者外周血单个核细胞核因子κB活性及血清炎症指标的影响。设计:自身前后对照。对象:2004-10/2006-06中山大学附属第二医院内分泌科住院和门诊收治的新诊断2型糖尿病患者29例。二甲双胍为中美上海施贵宝公司产品。方法:29例患者经筛选进入实验后,给予二甲双胍治疗,由1.0g/d开始,最大剂量2.0g/d。每2周随访1次,根据血糖水平调整药物剂量,血糖控制目标为空腹血糖<6.1mmol/L,餐后2h血糖<8mmol/L。分别于治疗前及血糖达良好控制0,2,12周时进行各项指标检查。主要观察指标:Westernblot法检测外周血单个核细胞磷酸化核因子κBp65(Ser536)水平,高敏ELISA法检测血清炎症指标的变化。结果:与治疗前比较,血糖达标2周时外周血单个核细胞中磷酸化核因子κBp65(Ser536)水平明显降低(P<0.05),至血糖达标12周时降低程度更为显著(P<0.01)。与治疗前比较,血糖达标时(0周)及达标后2周,12周,各项炎症指标水平均明显降低(P<0.05或0.01),其中血糖达标12周时超敏C反应蛋白降低56%,白细胞介素6降低30%,肿瘤坏死因子α降低24%。结论:二甲双胍可抑制新诊断2型糖尿病患者外周血单个核细胞中磷酸化核因子κB活性,显著改善患者炎症状态。BACKGROUND： IKK/nuclear factor κB pathway is the key pathway of macrophage secreted inflammatory factor, and can start and magnify inflammatory reaction. Metforrnin has potential anti-inflammation effects. OBJECTIVE： To investigate the effects of metformin on nuclear factor KB （NF-κB） activity in peripheral blood mononuclear cells and serum inflammation markers in patients with newly diagnosed Type 2 diabetes. DESIGN： The self controlled study. PARTICIPANTS： A total of 29 newly diagnosed type 2 diabetics were selected at the Department of Endocrinology, Second Affiliated Hospital, Sun Yat-sen University from October 2004 to June 2006. Metformin was purchased from Shanghai Shiguibao Co., Ltd. METHODS： All 29 patients underwent mefformin treatment （1.0 -2.0 g/d）. Follow-up was performed every two weeks. Drug dose was altered according to blood glucose levels. Blood glucose was controlled at fasting blood glucose 〈 6.1 mmol/L, 2-hour postprandial glucose 〈 8 mmol/L. Indexes were examined before treatment and at 0, 2 and 12 weeks after blood glucose was controlled. MAIN OUTCOME MEASURES： Phosphorylation status of NF-κB p65 （Set536） in peripheral blood was measured by Western blot. Serum inflammatory indexes were tested by enzyme linked immunosorbent assay, RESULTS： Compared with pre-treatment, the levels of phosphorylation NF-κB P65 decreased at 2 weeks after glucose control （P 〈 0.05）, and significantly reduced at 12 weeks （P 〈 0.01）. Compared with pre-treatment, inflammatory index levels were significantly reduced at 0, 2, 12 weeks after glucose control （P 〈 0.05 or 0.01）. The serum supersensitivity C reactive protein was decreased by 56%, interleukin-6 level was decreased by 30% and tumor necrosis factor-α level was decreased by 24% at 12 weeks after glucose control. CONCLUSION： Mefformin can inhibit phosphorylation status of NF-κB p65 （Set536） activity in peripheral blood and significantly improve inflammation in patients with newly diagnosed Type 2 diab

关 键 词：核因子ΚB 二甲双胍 2型糖尿病 炎症 

分 类 号：R394.2[医药卫生—医学遗传学]