严重烫伤小鼠TNF-α表达及其在胰岛素抵抗中作用的研究

Expression of TNF α and its role in insulin resistance after severe scalding in mice

目的：阐明ＴＮＦ－α超表达在烧伤胰岛素抵抗中的作用机制。方法：观察全层体表面积３０％（３０％ＴＢＳＡ）烫伤小鼠肝脏ＴＮＦ－αｍＲＮＡ表达的动态变化和肝脏及肌肉部分纯化的胰岛素受体酪氨酸蛋白激酶（Ｉｎｓｕｌｉｎｒｅｃｅｐｔｏｒｔｙｒｏｓｉｎｅｐｒｏｔｅｉｎｋｉｎａｓｅ，ＩｎｓＲ－ＴＰＫ）活性变化以及注射ＴＮＦ－ＭｃＡｂ后ＩｎｓＲ－ＴＰＫ活性恢复情况。结果：①严重烫伤小鼠肝脏ＴＮＦ－α－ｍＲＮＡ表达，伤后３ｈ开始升高，２４ｈ略有下降，随后又升高，一直持续到第５天。②严重烫伤小鼠肝脏和肌肉ＩｎｓＲ－ＴＰＫ活性降低。注射ＴＮＦ－ＭｃＡｂ，烫伤小鼠肌肉ＩｎｓＲ－ＴＰＫ活性恢复而肝脏ＩｎｓＲ－ＴＰＫ活性变化不明显。结论：严重烫伤后ＴＮＦ－αｍＲＮＡ表达增强，血中ＴＮＦ－α水平升高，抑制ＩｎｓＲ－ＴＰＫ活性。

Objective: To clarify the mechanism of the role of overexpression of TNF α mRNA in insulin resistance after severe scalding. Methods: In the mice inflicted with 30% TBSA full thickness skin scalding, the dynamic changes of TNF α mRNA expression in the liver and the activity of insulin receptor tyrosine protein kinase (InsR TPK) were determined. Then the reinstatement of InsR TPK activity by injecting TNF McAb for 3 days was also observed. Results: The expression of TNF α mRNA in the liver was markedly increased in the first 3h post scalding and remained high for 5 days. The activity of InsR TPK in both the liver and skeletal muscle with or without insulin stimulation was greatly reduced as compared with the control. In addition, these disorders of InsR TPK activity of muscle can be ameliorated through neutralization of the circulatory TNF α by administration of TNF McAb. Conclusion: The suppression of insulin receptor signal transmission due to the overecpression of TNF α mRNA and elevated circulatory TNF α level may be the molecular mechanism and central stage of insulin resistance after thermal injury.