外周血白细胞IKK-IκB-NFκB通路的激活与胰岛素抵抗关系的临床研究  

Clinical study on the relationship between the activation of the IKK-IκB-NFκB pathway and insulin resistance

作　　者：姚莉莉[1] 丁晓颖[1] 彭永德[1] 潘晓洁[1] 董维平[1] 

机构地区：[1]上海交通大学附属第一人民医院内分泌代谢科,200080

出　　处：《中华内分泌代谢杂志》2010年第9期770-773,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：上海市卫生局课题（44021）;上海市自然科学基金（04ZR14095）;上海市科委引导计划项目（74119638）

摘　　要：目的 探讨不同胰岛素敏感性个体炎症因子血浆水平以及炎症通路激活状态的差异.方法 收集体检女性38例,按体重指数分为两组：肥胖组22例,正常对照组16名,稳态模型评估的胰岛素抵抗指数（HOMA-IR）评估研究对象胰岛素敏感性,检测炎症因子白细胞介素6（IL-6）、IL-1β血浆水平,Western印迹法检测外周血白细胞IκB激酶（IKK）、NFκB抑制物（IκB）及其磷酸化水平,以凝胶电泳迁移率分析（EMSA）评价核因子NFκB的结合活性.结果 肥胖组空腹胰岛素[62.2（20.0～127.0）pmol/L对19.15（14.2～47.8）pmol/L,P〈0.01]、HOMA-IR[2.32（0.76～5.49）对0.70（0.53～1.7）,P〈0.01]、HbAIC[（5.42±0.45）%对（5.08±0.38）%,P〈0.05]、血甘油三酯[（1.75±0.68对1.22±0.58）mmol/L,P〈0.05]、IL-6[3.15（0.03～22.2）pg/ml对1.26（0.74～6.06）pg/ml,P〈0.01]和IL-1β[6.53（0.84～36）pg/ml对3.16（1.48-8.86）pg/ml,P〈0.01]水平显著高于正常对照组,伴随外周血白细胞胞浆蛋白IKKα、IKKβ表达和IκBα丝氨酸磷酸化水平增高,IκBα表达下调,肥胖组NFκB结合活性较正常对照组显著增加.结论 肥胖组炎症因子IL-6、IL-Iβ血浆水平显著升高.IKK-IκB-NFκB通路的激活与肥胖个体胰岛素抵抗的发生有关.Objective To explore the difference involved in the activation of inflammation pathway and the plasma level of inflammatory factors in the subjects with different sorts of insulin sensitivity. Methods The study was carried out in 38 women, consisting of obesity （n = 22 ） and control （n = 16 ） groups according to body mass index. The insulin sensitivity was assessed by homeostasis model assessment of insulin resistance （HOMAIR）. Plasma concentrations of interleukin-6 （II-6） and IL-1β were determined by enzyme immunoassay. Western blot analysis was used to examine total protein expression and phosphorylation levels of IκB kinase （IKK） ,inhibitor of nuclear factor-κB （ IκB ） in peripheral blood leukcocytes. Electrophoretic mobility shift assay （EMSA）was used to detect the binding activity of NFκB. Results The levels of fasting plasma insulin[62.2 （ 20.0-127. 0） pmol/L vs 19. 15 （ 14. 2-47. 8 ） pmol/L, P〈0. 01], HOMA-IR[2. 32 （ 0. 76-5.49 ） vs 0.70（0.53-1.7）,P〈0.0l], HbA1 C[（5.42±0. 45 ） % vs （ 5.08 ±0. 38） %, P〈0. 05], triglyceride[（ 1.75 ±0. 68 vs 1.22 ±0. 58 ）mmol/L, P〈0. 05], plasma IL-6[3. 15 （0. 03-22. 2） pg/ml vs 1.26 （0. 74-6.06 ） pg/ml, P〈0. 01], and IL-1 β[6. 53 （ 0. 84-36 ） pg/ml vs 3. 16（ 1.48-8. 86 ） pg/ml, P〈0. 01]in obesity group were significantly higher than those in control group. Compared with control group, the levels of IKKo, IKKβ expression and IκBα serine phosphorylation in obesity group were markedly increased, while the expression of IκBα was significantly reduced. Accompanied with the degradation of IκBα protein, the binding activity of NFκB in obesity group was significantly increased. Conclusions The plasma levels of IL-6 and IL-1β were significantly raised in obesity group. The activation of IKK-IκB-NFκB pathway is closely associated with the genesis and development of insulin resistance in obese subjects.

关 键 词：胰岛素抵抗 白细胞介素6 白细胞介素1β IΚB激酶 NFΚB 

分 类 号：R587.1[医药卫生—内分泌]