醋氨酚中毒致大鼠肝细胞的凋亡

Acetaminophen-induced apoptosis of hepatocyte in rats

目的 探讨醋氨酚中毒大鼠肝组织中Fas、Fas L的表达与醋氨酚药物剂量之间的关系 ,以及醋氨酚药物剂量与肝细胞凋亡之间的关系。方法 采用免疫组化方法对醋氨酚中毒大鼠肝组织中Fas、Fas L的表达进行检测 ;应用末端原位标记法对大鼠的肝细胞凋亡进行检测。结果 醋氨酚中毒剂量与Fas/FasL表达之间关系密切 (P <0 0 1 ) ,醋氨酚剂量越大 ,Fas/FasL表达越强。同时 ,醋氨酚中毒剂量与肝细胞凋亡之间也关系密切 (P <0 0 1 ) ,醋氨酚剂量越大 ,凋亡细胞数目也越多。结论 醋氨酚介导的Fas和FasL表达在肝细胞凋亡和坏死中起重要作用 ,肝细胞的直接自杀或自分泌及旁分泌杀伤机制 ,可能是醋氨酚中毒致肝细胞凋亡和坏死的重要发病机制之一。

Objectives To investigate the relationship between expression of Fas/Fas ligand(FasL) and dose of acetaminophen;the relationship between dose of acetaminophen and number of apoptotic cells in acetaminophen induced liver damage in rat.Methods Fas/FasL expression was determined by liver transferase mediated dUTP nick end labeling techniques(TUNEL test).Results We found that there was a close relationship between expression of Fas/Fas ligand and dose of acetaminophen( P <0 01):the higher the dose of acetaminophen,the stronger Fas/FasL expression.And there also was a similar positive relationship between dose of acetaminophen and the number of apoptotic cells( P <0 01).Conclusion Expression of Fas and FasL in hepatocytes induced by acetaminophen may play important roles in apoptosis and death of hepatocytes.Damage of hepatocytes probably occurred by autocrine or paracrine and fratricide mechanisms mediated by the hepatocytes themseves.It is one of the impotant pathogenesis mechanisms that results in hepatocyte necrosis induced by acetaminophen. [