中文摘要：

目的：通过注射内毒素（LPS）建立的大鼠脓毒症模型,观察胰岛素不同时机给药对血清和肝细胞因子表达的影响。方法：将81只大鼠分为九组,即A组腹腔注射等渗盐水;B组腹腔注射LPS;C、D、E、F、G、H、I组分别在腹腔注射LPS前30 min和注射后0、1、3、6、12、24 h给予胰岛素治疗。观察各组大鼠LPS注射后24和48h血清白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）和IL-10的变化,以及LPS注射48 h后肝组织IL-1β、IL-6、TNF-α和IL-10的变化。结果：注射LPS后24和48 h,大鼠血IL-1β、IL-6、TNF-α和IL-10均显著增加。LPS注射48 h后,肝组织中IL-1β、TNF-α、IL-6和IL-10蛋白水平也明显增加。在注射LPS前30 min或注射后6 h内给予胰岛素,能明显降低注射后24和48 h血清中的IL-1β、TNF-α和IL-6水平（P〈0.05）;而IL-10水平则仅在注射LPS前或注射同时给予胰岛素,才较LPS组明显增加（P〈0.05）。在LPS注射前30 min或注射后6 h内给予胰岛素,注射后48 h肝内的IL-1β和TNF-α水平较LPS组明显降低（P〈0.05）;而肝的IL-6水平仅在LPS注射前30min或与同时给予胰岛素时,才较LPS组明显降低（P〈0.05）。结论：胰岛素对脓毒症大鼠有抑制炎性细胞因子,增加抗炎介质释放等保护作用。在注射LPS 6 h内给予胰岛素可发挥良好的抗炎保护作用,而在注射LPS 6 h后给予胰岛素治疗其抗炎保护作用明显减弱。

英文摘要：

Objective： The aim of the present study was to determine whether timing of insulin administration influences the hepatic and serum proinflammatory and anti-inflammatory cytokines during endotoxemia stimulated by LPS.Methods： 81 Male Sprague Dawley rats were divided in 9 groups： Group A was sham control group（rats were treated with saline and without insulin or LPS）;Group B was LPS group（rats were treated with LPS and without insulin）;In Group C,D,E,F,G,H and I,insulin was given on 30 min pre LPS administrated and hour 0,1,3,6,12 and 24hr after the induction of endotoxemia,in respectively.Hepatic and serum proinflammatory cytokines IL-1β,IL-6 and TNF-α,and antiinflammatory cytokines IL-10 were detected on 24 and 48 hours after the induction of endotoxemia.Results： Compared with sham control rats,serum concentrations of proinflammatory cytokines IL-1β,IL-6 and TNF-α and anti-inflammatory cytokine IL-10 were significantly increased on 24 and 48 hrs after induction of endotoxemia.Similarly,LPS administration also significantly increased the hepatic IL-1β,TNF-αIL-6 and IL-10 protein concentration on 48 hrs after LPS injection.Compared with levels in endotoxemic animals receiving saline,on 24 and 48hrs after LPS injection,insulin administrated ahead of 6hrs after LPS injection significantly decreased the serum IL-1β,IL-6 and TNF-α concentration（P〈0.05）,and significantly increased anti-inflammatory cytokine IL-10 concentration（P〈0.05）;And,hepatic IL-1β and IL-6 expression were（P〈0.05） significantly decreased compared with levels in endotoxemic animals receiving saline.But,the significant decrease of hepatic TNF-α expression and significant increase of hepatic IL-10 were only seen in the animals in which insulin was administrated at 30mins pre LPS or coadministrated with LPS.Insulin administrated post of 6 hrs after LPS injection lost the ability to significantly reduced serum or hepatic IL-1β,TNF-α,and IL-6 concentration.Conclusion： Insulin has a protective role in systemi