c-Jun氨基末端激酶在烧伤后胰岛素抵抗中作用的实验研究  

Role of c-Jun NH(2)-terminal kinase in insulin resistance after burn

作　　者：陈新龙[1] 夏照帆[2] 韦多[2] 贲道锋[2] 唐洪泰[2] 葛绳德[2] 

机构地区：[1]武警医学院附属医院烧伤整形科,天津300162 [2]第二军医大学附属长海医院烧伤科

出　　处：《中华外科杂志》2007年第1期62-64,共3页Chinese Journal of Surgery

基　　金：国家自然科学基金(30571921);国家973项目(G1999054309);国家863项目(2001AA21604)

摘　　要：目的探讨 c-Jun 氨基末端激酶(c-Jun NH(2)-terminal kinase,JNK)在烧伤后胰岛素抵抗中的作用及其机制。方法将24只 SD 大鼠随机分为对照组、烧伤组和烧伤+anisomycin 组。烧伤组和烧伤+anisomycin 组大鼠制成30%总体表面积(TBSA)三度烧伤模型。烧伤+anisomycin 组大鼠伤后第4天静脉注射 anisomycin[5 mg/kg,溶于250μl二甲基亚砜(DMSO)],其余两组静脉注射250μl DMSO,2 h 后进行正常血糖高胰岛素钳夹技术实验,然后采集肌肉标本,采用免疫沉淀和免疫印迹观测肌肉组织胰岛素受体底物1丝氨酸307(IRS-1 Ser307)磷酸化和酪氨酸活性变化并观察肌肉组织磷酸化 JNK 的差异。结果正常血糖高胰岛素钳夹技术实验中对照组、烧伤组和烧伤+anisomycin 组10%葡萄糖输注率(mg·kg^(-1)·min^(-1))分别为12.3±0.4,6.6±0.3,6.5±0.4。烧伤后肌肉组织 IRS-1磷酸化丝氨酸307活性明显升高,而 IRS-1磷酸化酪氨酸活性明显降低,磷酸化 JNK活性升高。结论 JNK 通过增加烧伤大鼠 IRS-1磷酸化丝氨酸307活性,至少部分参与了烧伤后胰岛素抵抗。Objective To investigate the role of c-Jun NH（2）-terminal kinase （JNk） in insulin resistance after burn and its mechanism. Methods Twenty-four Sprague-Dawley rats were randomized to control, burn and burn ＋ anisomycin groups. The rats in control group received sham burn trauma, and burn and burn ＋ anisomycin groups received 30% total bady surface area （TBSA） full thickness burn injury. Anisomycin （5 mg/kg） together with 250 μl dimethyl sulfoxide （DMSO） was injected to the rats in anisomycin group intravenously, and only 250 μl DMSO in the other two groups. Euglycemichyperinsnlinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phuspho-tyrosine of insulin receptor substrale （IRS）-1 and phuspho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups. Results The infusing rates of total 10% glucose （ mg · kg^-1 · min^-1 ） in control, burn and burn ＋ anisomycin group were 12.3 ± 0. 4, 6. 6 ± 0. 3, 6. 5 ± 0. 4, respectively. The level of IRS-1 Serine307 phusphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phusphorylation of IRS-1 decreased markedly after burn. Conclusions The activation of JNK elevates the level of IRS-1 phuspho-serine 307 and might play a role in insulin resistance after burn in rats.

关 键 词：烧伤 胰岛素抵抗 c—Jun氨基末端激酶 

分 类 号：R644[医药卫生—外科学] R587.1[医药卫生—临床医学]