摘要
目的:观察脓毒症大鼠急性肝损伤时肝脏Toll样受体4(TLR4)和肿瘤坏死因子α(TNF-α)水平的变化,探讨还原型谷胱甘肽(GSH)对脓毒症大鼠急性肝损伤的保护作用及其机制。方法:采用盲肠结扎穿孔术(CLP)制备SD大鼠脓毒症肝损伤模型。实验大鼠随机分成假手术组、模型组、GSH干预组(每组各24只),每组大鼠再按按0h、2h、6h、24h分为4个亚组(每组各6只)。GSH干预组在造模后立即经尾静脉给予GSH(300mg.kg-1)共0.1mL,假手术组和模型组则给予等量0.9%氯化钠溶液。每组大鼠在4个时间点(CLP术后0h、2h、6h、24h)采集血标本和肝组织标本。HE染色观察肝组织病理改变;检测血清肝功能和肝组织TLR4和TNF-α水平的变化。结果:与假手术组相比,模型组大鼠血清肝功能水平在术后6h起开始升高,术后24h仍持续升高;肝组织TLR4和TNF-α水平均在术后2h显著升高,术后6h达到高峰,术后24h有所回落;术后24h肝组织HE染色显示肝细胞肿胀、大量炎性细胞浸润、细胞变性等损伤性改变。与模型组相比,GSH干预组在术后6h和24h血清肝功能损伤指标显著降低(P<0.05),而肝组织TLR4和TNF-α水平在术后2h、6h、24h均显著降低(P<0.05),肝组织的病理学损伤性改变也明显减轻。结论:在脓毒症早期肝组织TLR4及其调控的炎性因子TNF-α水平增高在脓毒症急性肝损伤中起重要作用;脓毒症早期应用GSH治疗可能通过降低TLR4水平,减少肝组织TNF-α浓度,对脓毒症急性肝损伤有保护作用。
Objective： Based on the potent antioxidant effects of glutathione（GSH）,we investigated the putative protective role of GSH by the level of TLR4 and that of TNF-α in liver against sepsis-induced hepatic injury in rats.Methods： Sepsis-induced hepatic injury was induced by cecal ligation and puncture（CLP） in SD rats.Rats were randomly divided into 3 groups,which were sham group,CLP group and GSH treatment group（n=24）.Rats of each group were sacrificed at the time point of 0 h,2 h,6 h and 24 h after the operation（n=6）.Rats of GSH group were intravenously administered with GSH（300 mg/kg-1） after the operation and the rats of other two groups were treated with same dose saline.The samples of blood and liver tissues were harvested at each time point.TLR4 and tumor necrosis factor-alpha（TNF-α） in liver tissues were examined by ELISA kits and histological alterations by HE staining.Results： Sepsis resulted in an increase in total bilirubin（TBIL）,direct bilirubin（DBIL） and alanine aminotransferase（ALT） levels at 6 h after operation and persistent increase at 24 h.There was an increase in TLR4 levels at 2 h after operation,up to top 6 h and slight decrease at 24 h.The same results were observed in TNF-α levels.The hepatic injury was confirmed by histological examination.The increases of ALT/DBIL/TBIL in serum were attenuated by GSH at 6 h and 24 h after operation.Meanwhile,GSH could reversed the TNF-α and TLR4 levels and the microscopic damage,demonstrating its protective effects against sepsis-induced hepatic injury（P0.05）.Conclusions： The increased TLR4/TNF-α levels have an important role in the sepsis-induced hepatic damage.GSH ameliorates hepatic injury by suppressed TLR4/TNF-α levels in liver tissue.Thus,supplementing antiseptic hepatic injury treatment with GSH may be beneficial in the clinical setting.
出处
《中国临床医学》
2010年第5期667-670,共4页
Chinese Journal of Clinical Medicine
