文献类型：期刊文献

中文题名：IL-18、TNFα在脂多糖介导的急性肝坏死发生中的作用研究

英文题名：Study on the role of IL-18 and TNF-α in lipopolysaccharide-mediated acute hepatic necrosis

作者：晏春根[1];谢青[2];徐玉敏[2];周霞秋[2];俞红[2];郭清[2]

机构：[1]浙江绍兴文理学院医学院;[2]上海第二医科大学附属瑞金医院感染科

年份：2003

卷号：8

期号：2

起止页码：21

中文期刊名：肝脏

外文期刊名：Chinese Hepatology

收录：CSTPCD

语种：中文

中文关键词：急性肝坏死;白细胞介素-18;肿瘤坏死因子α;mRNA;ELISA

外文关键词：Lipopolysaccharide; IL 18; TNFα; Acute hepatic necrosis

中文摘要：目的　探讨IL 18、TNFα在急性肝损伤中的作用。方法　采用D 氨基半乳糖 (D Gal) 90 0mg/kg与脂多糖(LPS) 10 μg/kg诱导BALB/C小鼠急性肝坏死动物模型 ,腹腔内注入D Gal/LPS后 0～ 9h分别检测血清转氨酶 (ALT、AST)、肝组织病理、DNA梯形条带 ,评估肝损伤情况 ;用半定量RT PCR和相应的分析软件分析不同时间点肝组织中IL 18mRNA、TNFαmRNA表达及ELISA试剂盒检测血浆IL 18、TNFα的蛋白表达。结果　D Gal/LPS给予后 4h血清转氨酶明显升高 ,7h小鼠开始死亡 ,10h死亡率达 80 %。肝组织病理学检查发现 ,5h肝窦扩张、炎性细胞浸润、库普弗细胞增生 ;7h肝细胞大量凋亡、坏死或肝组织出现大量出血性坏死 ;5h电镜示肝细胞核仁碎裂、线粒体肿胀或空泡变性 ;7h核仁边聚 ,呈半月型 ,表现为典型的凋亡形态学变化 ,线粒体大部分空泡变性。DNA电泳显示 5h始出现梯形条带。正常情况下肝组织IL 18mRNA少量表达 ,经D Gal/LPS诱导后小鼠肝组织IL 18mRNA表达量明显增加 ,表达高峰在LPS刺激后 1～ 2h(与 0h比较 ,P <0 .0 1) ;正常情况下肝组织TNFαmRNA不表达或呈微弱表达 ,但在该模型诱导过程中肝组织TNFαmRNA有不同程度的表达 ,且其表达的时间模式与IL 18mRNA不同 ,TNFαmRNA表达高峰见于LPS刺激后 2h和 5h(与 0h比较 。

外文摘要：Objective To appraise the role of IL 18 and TNF α in acute hepatic necrosis. Methods The animal model of acute hepatic necrosis is induced by D galactosamine(D Gal, 900mg/kg)and lipopolysaccharide(LPS, 10μg/kg). To evaluate the hepatic injury of this animal model, we detected the serum transaminases(ALT and AST),the liver histopathology and the DNA ladder at the time points from 0h to 9h after intraperitoneal injection of D Gal/LPS. The expressions of IL 18 mRNA and TNF α mRNA and their corresponding proteins were detected by semiquantitative RT PCR and ELISA kit and analyzed by their corresponding software.Results After 4 hrs of intraperitoneal injection of D Gal/LPS ,the serum transaminase and plasma TNF α levels were apparently elevated. The treated mice began to die 7 hrs afterwards. The mortality rate reached to 80% at 10 hrs . The histopathology showed dilatation of liver sinusoids, infiltration of inflammatory cells and proliferation of Kupffer cells at 5 hrs, with subsequent hepatocytes apoptosis and necrosis . At the late stage more and more hepatocytes became necrotic. The DNA ladder was shown in electrophoresis after 5 hrs of D Gal/LPS injection. IL 18mRNA and TNF α mRNA were expressed at low level in normal mice liver, the IL 18mRNA increased significantly and maintained at higher level following intraperitoneal injection with D Gal/LPS (compared to 0h time point, P <0.05)and TNF α mRNA also increased and up to the peak at 2hs and 5hs(compare to 0h, P <0.01). Similar results were obtained with plasma IL 18 and TNF α proteins.Conclusion The apoptosis and necrosis of hepatocytes are present concomitantly in this animal model. The expression of IL 18mRNA、TNF α mRNA increased apparently in the liver after intraperitoneal injection with D Gal/LPS. The changes of transaminase and histopathyology appear later than that of IL 18mRNA、TNF α mRNA and their corresponding proteins. Furthermore, the occurrance of expression of IL 18 mRNA precedes that of TNF αmRNA.It is suggested that IL 18、TNF α are all involved in this hepatic injury animal model and IL 18 maybe the upper stream cytokine of TNF α.