【摘要】 研究显示急性肝衰竭(AHF)与肝细胞凋亡密切相关,而Smac/DIABLO是线粒体凋亡途径的重要促进因子。目的:动态观察AHF模型大鼠肝组织中Smac/DIABLO、caspase-3的表达变化,探讨两者的变化在AHF中的意义。方法:以D-半乳糖胺腹腔注射诱导大鼠AHF模型,于造模后12h、24h、48h、72h、120h、168h和240h分批处死大鼠,以RT-PCR和免疫组化方法检测肝组织Smac/DIABLO、caspase-3 mRNA和蛋白表达,同时检测血清肝功能指标。结果:AHF模型建立后,大鼠血清ALT、AST、总胆红素水平迅速升高,白蛋白水平则明显下降,于48h或72h后逐渐好转。模型大鼠肝组织中Smac/DIABLO、caspase-3 mRNA和蛋白表达随病情加重而逐渐增强,于72h时达高峰,其后随病情好转而逐渐下降,其蛋白表达在中央静脉周围、门管区和坏死区周围最为明显。结论:AHF模型大鼠肝组织中Smac/DIABLO、caspase-3的表达随疾病进程而波动,观察其表达变化有利于AHF预后的判断。抑制Smac/DIABLO在线粒体凋亡途径中的作用,为AHF的治疗提供了新的思路。更多还原

【Abstract】 Background: It has been reported that acute hepatic failure (AHF) is closely correlated with apoptosis of hepatocytes. Smac/DIABLO is an important promoter in mitochondrial apoptotic pathway. Aims: To investigate the dynamic expressions of Smac/DIABLO and caspase-3 in liver tissue of AHF model rats and their significance. Methods: AHF model was induced by D-galactosamine intraperitoneal injection in rats. The model rats were killed at 12, 24, 48, 72, 120, 168 and 240 hours after model construction, respectively. The mRNA and protein levels of Smac/DIABLO and caspase-3 in liver tissue were determined by RT-PCR and immunohistochemistry, the serum indices of liver function were analyzed simultaneously. Results: The serum levels of ALT, AST and total bilirubin increased and the serum level of albumin decreased rapidly after model construction, all of these indices improved gradually 48 or 72 hours later. The mRNA and protein levels of Smac/DIABLO and caspase-3 in liver tissue of model rats increased and got the peak at 72-hour time point with the aggravation of AHF, and then decreased with the recovery of AHF. The immunopositivity of Smac/DIABLO and caspase-3 mainly distributed in areas surrounding the central vein and foci of necrosis, as well as in portal area. Conclusions: The expression levels of Smac/DIABLO and caspase-3 in liver tissue are parallel with the natural history of AHF in model rats, which might be used as a prognosis predictor of AHF. Inhibition of Smac/DIABLO in mitochondrial apoptotic pathway might offer a novel potential approach for the treatment of AHF.更多还原