还原型谷胱甘肽对脓毒症大鼠肝损伤时肝组织热休克蛋白70的影响  

Influence of glutathione on heat shock protein 70 level of liver in sepsis - induced hepatic injury in rats

作　　者：陈斌[1] 童朝阳[1] 杜施霖[1] 施东伟[1] 黄培志[1] 

机构地区：[1]复旦大学附属中山医院急诊科,上海200032

出　　处：《中国急救医学》2010年第8期728-732,共5页Chinese Journal of Critical Care Medicine

摘　　要：目的通过观察还原型谷胱甘肽（GSH）对脓毒症大鼠急性肝损伤时肝组织热休克蛋白70（HSP70）和肿瘤坏死因子-α（TNF-α）水平的影响，探讨GSH对脓毒症大鼠急性肝损伤的保护作用及其可能的机制。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），每组大鼠再随机分为0、2、6、24h4个亚组（每组各6只）。GSH干预组在造模后立即经尾静脉给予GSH300mg／kg（0．1mL），假手术组和模型组则给予等量生理盐水。每组大鼠在CLP术后0、2、6、24h分别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HSP70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（TBIL、ALT和AST）水平在术后6h起开始升高，术后24h仍持续升高；肝组织HSP70水平在术后2h即显著升高，术后6h达到高峰，术后24h则有所回落；肝组织TNF-α水平在术后2h起开始升高，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及肝组织TNF-α水平显著降低（P〈0．05），而肝组织HSP70水平在术后2h、6h和24h均显著升高（P〈0．05）；术后24h肝组织的病理学损伤性改变明显减轻。结论在脓毒症早期应用GSH治疗对脓毒症急性肝损伤有保护作用；其作用机制可能是通过提高肝组织HSP70浓度，降低肝组织TNF-α浓度，从而减轻炎性因子对肝组织的损伤。Objective Based on the potent antioxidant effects of glutathione （GSH）, we investigated the putative protective role of GSH by the level of heat shock protein 70 （HSP70） and that of tumor necrosis factor-α （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, 2, 6 and 24 h after the operation （ n =6）. Rats of GSH group were intravenously administered with GSH （300 mg/kg） after the operation and the rats of other two groups were treated with same dose saline. The rats were separately killed 0, 2, 6 or 24 h after the operation. The samples of blood and liver tissues were collected for level of TNF-α and HSP70, histological alterations and biochemical changes. Results Sepsis resulted in an increase in TBIL, ALT and AST levels 6 h after operation and persistent increase 24 h. There is an increase in HSP70 levels 2 h after operation, up to top 6 h and slight decrease 24 h. The same results were observed in TNF -α levels. The hepatic injury was confirmed by histological examination. Compared with model group, GSH group clearly reversed the TNF -α and HSP70 levels and the microscopic damage, demonstrating its protective effects against sepsis - induced hepatic injury （ P 〈 0.05 ）. Conclusion The increased TNF -α levels and decreased HSP70 levels were related with sepsis - induced hepatic damage. GSH ameliorated hepatic injury by suppressed TNF -α expression and increase HSP70 levels in liver tissue. Thus, supplementing antiseptic hepatic injury treatment with GSH may be beneficial in the clinical setting.

关 键 词：还原型谷胱甘肽 脓毒症 肝损伤 热休克蛋白70 肿瘤坏死因子-α 

分 类 号：R575[医药卫生—消化系统]