内毒素血症小鼠肝脏TNFα的表达及其意义

EXPRESSION OF TNFα mRNA IN LIVER AFTER ENDOTOXEMIA IN MICE AND ITS SIGNIFICANCE

目的 探讨肝脏肿瘤坏死因子α(TNFα)mRNA表达在内毒素血症反应中的作用。方法 动态观察腹腔注射脂多糖 (LPS)小鼠血浆TNFα含量、肝脏TNFαmRNA表达以及肝脏和肌肉 2 脱氧葡萄糖摄取的改变。结果 与对照组比较 ,腹腔注射脂多糖 3小时后 ,小鼠血浆TNFα水平明显升高 ,并持续到 3天后 ;肝脏TNFαmRNA表达亦于 3小时后明显升高 ,并与血浆TNFα改变相平行 ;肝脏及肌肉基础葡萄糖摄取增强 ,但对胰岛素刺激葡萄糖摄取的反应性明显降低 ,而且这些改变可被肿瘤坏死因子α单克隆抗体 (TNFα McAb)部分纠正 ,但肝脏恢复效果不如肌肉明显。结论 内毒素血症时肝脏TNFαmRNA表达增强 ,抑制葡萄糖摄取 ,在创伤。

Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. [WT5”HZ]Methods [WT5”BZ]In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2 deoxyglucose (2 DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. [WT5”HZ]Results [WT5”BZ]The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2 DG both in muscle and liver were markedly increased, but the stimulated 2 DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2 DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF McAb. [WT5”HZ]Conclusion [WT5”BZ] The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia