胰岛素受体底物1在烧伤后胰岛素抵抗中的作用  

Role of insulin receptor substrate 1 in insulin resistance after burn

作　　者：陈新龙[1] 夏照帆[1] 韦多[1] 田建广[1] 郇京宁[1] 路卫[1] 唐洪泰[1] 朱世辉[1] 

机构地区：[1]第二军医大学长海医院烧伤科,上海200433

出　　处：《第二军医大学学报》2004年第10期1052-1054,共3页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金 ( 3 0 2 713 40 ) ;国家重点基础研究规划 ("973"计划 )课题 ( G19990 5 43 0 9) ;国家高新技术发展规划("863"计划 )课题 ( 2 0 0 1AA2 160 4)

摘　　要：目的 :观察烧伤后胰岛素受体底物 1(IRS- 1)及其丝氨酸 30 7和酪氨酸磷酸化的变化 ,探讨烧伤后胰岛素抵抗的分子机制。方法 :6周龄 SD大鼠 (体质量 16 0～ 170 g)随机分为假烫伤组 (n=8)和烫伤组 (n=8) ,烫伤组大鼠制成烧伤面积为 30 %的 度烫伤模型 ,伤后第 4天 ,禁食 5 h后的大鼠 ,进行正常血糖高胰岛素钳夹技术实验 ,实验后颈动脉放血处死 ,立即采集肌肉和脂肪标本 ,采用免疫沉淀和免疫印迹方法分析 IRS- 1及其丝氨酸 30 7和酪氨酸磷酸化的变化情况。 结果 :烫伤后肌肉和脂肪组织中 IRS- 1上丝氨酸 30 7磷酸化水平显著升高 [假烫伤组光密度值设定为 1,进行对照比较 ;骨骼肌 :(3.78± 1.5 8) vs(1.0 0± 0 .16 ) ,P<0 .0 1;脂肪组织 :(2 .0 9± 0 .4 4 ) vs(1.0 0± 0 .18) ,P<0 .0 5 ],而 IRS- 1上酪氨酸磷酸化水平显著降低 [骨骼肌 :(0 .6 6± 0 .32 ) vs(1.0 0± 0 .34) ,P<0 .0 5 ;脂肪组织 :(0 .6 2± 0 .2 7) vs(1.0 0± 0 .2 4 ) ,P<0 .0 5 ]。烫伤后 IRS- 1含量无显著性改变 [肌肉组织 :(0 .87± 0 .0 5 ) vs(1.0 0± 0 .17) ,P>0 .0 5 ;脂肪组织 :(0 .93± 0 .0 1) vs(1.0 0± 0 .16 ) ,P>0 .0 5 ]。结论 :烧伤后 IRS- 1丝氨酸 30Objective:To investigate the changes of insulin receptor substrate 1(IRS-1),Serine 307 and tyrosine phosphorylation of IRS-1 after burn,providing information for the molecular mechanism of insulin resistance after burn. Methods:Sprague-Dawley rats were randomized into burn group (n=8):30%TBSA full thickness burn injury and control group (n=8):sham burn trauma. IRS-1,phospho-Serine 307 and phospho-tyrosine of IRS-1 in skeletal muscles and fat tissues after Euglycemic-Hyperinsulinemic glucose clamps in vivo were determined by immunoprecipitation and Western blot analysis. Results:The level of IRS-1 Serine 307 phosphorylation in both skeletal muscles and fat tissues increased significantly in burn group compared with that in control group (Skeletal muscle:3.78±1.58 vs 1.00±0.16,P<0.01;Fat tissue:2.09±0.44 vs 1.00± 0.18, P< 0.05), while insulin-induced tyrosine phosphorylation of IRS-1 decreased significantly in burn group compared with that in control group (Skeletal muscle:0.66±0.32 vs 1.00±0.34,P<0.05;Fat tissue:0.62±0.27 vs 1.00± 0.24, P< 0.05). But quantities of IRS-1 were not significantly different between 2 groups (Skeletal muscle:0.87±0.05 vs 1.00± 0.17, P>0.05;Fat tissue:0.93±0.01 vs 1.00±0.16,P>0.05). Conclusion:This study indicates that Serine 307 hyper-phosphorylation and tyrosine hypo-phosphorylation of IRS-1 in vivo may be an important molecular mechanism of insulin resistance after burn.

关 键 词：烧伤 胰岛素抵抗 胰岛素受体底物1 丝氨酸307 酪氨酸 磷酸化 

分 类 号：R644[医药卫生—外科学]