中文摘要：

目的探讨肿瘤坏死因子α（TNF-α）诱导的胰岛素抵抗（IR）对小鼠糖脂代谢相关细胞因子的影响。方法用静脉葡萄糖耐量试验和3-[^3HI葡萄糖为示踪剂的扩展胰岛素钳夹技术评价不同TNF-α剂量组及对照（NC）组小鼠胰岛素敏感性和糖脂代谢的变化，用RT-PCR、western blot和ELISA测定脂联素和内脏脂肪素表达水平的变化。结果HTNF-α组小鼠FBG、Ins、FFA水平及糖耐量和胰岛素释放水平变化较MTNF-α和LTNF-α组更明显。胰岛素钳夹术中，与NC组相比，HTNF-α组Ins对FFA的抑制作用明显障碍，葡萄糖输注率明显降低，基础葡萄糖清除率（GRd）和肝糖输出率（HGP）明显升高。钳夹稳态时，HTNF-α组GRd的增加明显低于NC组，NC组HGP被完全抑制，而HTNF-α组仅被部分抑制。HTNF-α组脂肪组织脂联素和内脏脂肪素mRNA表达及血浆脂联素和内脏脂肪素水平也明显低于NC组。结论脂联素、内脏脂肪素的变化在TNF-α诱导的IR中可能具有重要作用。

英文摘要：

Objective To investigate the effect of TNF-α induced insulin resistance （IR） on glucoselipid metabolism-related cytokines in mice. Methods The insulin sensitivity and glucose-lipid metabolism in awake mice groups with high, middle, low dose of TNF-α treatment （HTNF, MTNF, LTNF） and in NC group were evaluated by intravenous glucose tolerance test （IVGTT） and hyperinsulinemic-euglycemic clamp technique combined with 3-PHI glucose as a tracer. The expression states of genes （such as adiponectin and visfatin） were measured by RT-PCR, Western blot and ELISA. Results Changes of fasting blood glucose （FBG）,plasma insulin and free fatty acids （FFA）,glucose tolerance and the insulin release of glucose-stimulation were more significantly in H group than in M or L group. During hyperinsulinemic-euglycemic clamp,the suppressive effect of insulin on FFA was significantly blunted （P 〈0. 01 ）, glucose infusion rate （GIR） was significantly decreased （P 〈 0. 01 ）, and basal glucose disappearance rate （GRd） and hepatic glucose production （HGP） were significantly increased （P〈0. 01） in H group compared with NC group. During steady-state, the GRd increasing in TNF group was still lower compared with NC group （P〈0. 01）, HGP was completely suppressed in NC group, but partly in H group. The adiponectin and visfatin mRNA expressions of adipose tissues were significantly decreased compared with NC group（P〈0. 01 and P〈0.05, respectively）, and plasma adiponectin and visfatin in TNF group were also reduced （both P 〈 0. 01）. Conclusions Adiponectin and visfatin might play an important role in TNF-α-induced insulin resistance.