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[四氯化碳诱导大鼠急性肝损伤中Fas抗原和Fas配体的表达]

[Expression of Fas antigen and Fas ligand in acute liver injury induced by carbon tetrachloride in rat].

作者信息

Wen Tao, Ren Feng, Liu Yan, Wu Zhi-ming, Zhao Jin-yuan

机构信息

Institute of Hepatitis, Youan Hospital, Capital University of Medical Sciences, Beijing 100069, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006 Jul;18(7):417-20.

Abstract

OBJECTIVE

To investigate the dynamics of expression of Fas antigen and Fas ligand (FasL) in a rat model of carbon tetrachloride-induced acute liver injury, and explore the role of apoptosis in liver injury.

METHODS

Thirty-five healthy male Wistar rats were randomly divided into normal control group and experiment group, and the latter group was divided into six subgroups: 3, 9, 16, 24, 36 and 48 hours groups with 5 rats in each group. The liver injury was induced by carbon tetrachloride. Sections of liver tissue were stained with hematoxylin and eosin and observed under optical microscope. Fas antigen and FasL in rat liver were determined at different time points with immunohistochemical method. Hepatocytes apoptosis were observed with terminal deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling (TUNEL) method. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in the liver tissues were analyzed at the same time point. Serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were also determined.

RESULTS

Fas antigen and FasL were expressed in the liver tissues of control rats. Following carbon tetrachloride challenge, severe liver injury took place in rats as revealed under microscope and a large amount of hepatocytes apoptosis was found. Hepatic Fas and FasL expression were both increased markedly from 3 to 48 hours after carbon tetrachloride challenge in experiment group. Liver MDA concentration and serum ALT and AST were elevated significantly, while SOD activity decreased remarkably in the experiment group compared with control group (P<0.05 or P<0.01).

CONCLUSION

Expression of Fas/FasL is remarkably induced in acute liver injury and accords with the changes of hepatocytes apoptosis, which suggests that apoptosis mediated by Fas/FasL may play an important role in the pathogenesis of acute liver injury.

摘要

目的

研究四氯化碳诱导的大鼠急性肝损伤模型中Fas抗原和Fas配体(FasL)的表达动态变化,探讨细胞凋亡在肝损伤中的作用。

方法

将35只健康雄性Wistar大鼠随机分为正常对照组和实验组,实验组再分为6个亚组:3小时组、9小时组、16小时组、24小时组、36小时组和48小时组,每组5只大鼠。采用四氯化碳诱导肝损伤。肝组织切片进行苏木精-伊红染色,在光学显微镜下观察。采用免疫组织化学方法在不同时间点检测大鼠肝脏中的Fas抗原和FasL。采用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(TUNEL)法观察肝细胞凋亡情况。同时分析肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)浓度。还测定血清天冬氨酸氨基转移酶(ALT)和丙氨酸氨基转移酶(AST)水平。

结果

对照组大鼠肝脏组织中表达Fas抗原和FasL。四氯化碳攻击后,大鼠出现严重肝损伤,显微镜下可见大量肝细胞凋亡。实验组在四氯化碳攻击后3至48小时,肝脏Fas和FasL表达均显著增加。与对照组相比,实验组肝脏MDA浓度、血清ALT和AST显著升高,而SOD活性显著降低(P<0.05或P<0.01)。

结论

急性肝损伤时Fas/FasL表达明显上调,且与肝细胞凋亡变化一致,提示Fas/FasL介导的细胞凋亡可能在急性肝损伤发病机制中起重要作用。

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