慢性乙醇中毒所致大鼠肝损伤和肝细胞凋亡

Liver injury and hepatocyte apoptosis induced by chronic alcoholic intoxication in rats

目的:研究肝细胞凋亡在实验性大鼠乙醇性肝病(ALD) 发生、发展中的作用．方法:给大鼠饮用220 g／L的乙醇,并结合540 g／L乙醇分次、少量灌胃的方法建立大鼠肝损伤模型;常规HE 染色,光镜观察大鼠病理学形态改变,用TUNEL法检测肝细胞凋亡,速率法检测血清ALT,AST水平．结果:灌乙醇5 wk大鼠肝脏出现轻到中度脂肪变性,脂滴为以大泡型为主的混合脂滴,脂变率为40％(8／20); 10 wk,85％(17／20)大鼠发生肝脂肪变,45％(9／20)大鼠出现乙醇性肝炎的病理变化．5,10 wk大鼠血清 ALT,AST均较同期对照组有显著升高(5 wk:1017 ±267 VS 550±133,P<0．05;1350±333 vs 967±150, P<0．05;10 wk:1500±267 vs 767±250．P<0．05;2167 ±533 vs 850±183,P<0．05);灌乙醇10 wk血清ALT, AST较5 wk升高(P<0．05),有统计学意义．5,10 wk大鼠 TUNEL指数分别为0．33±0．49％、2．03±1．61％,与同期对照组相比,5 wk无显著差异,10 wk有显著性差异 (P<0．05);灌乙醇10 wk TUNEL指数较5 wk高,有显著性差异(P<0．05)．按病理损伤程度,将实验组分成乙醇性肝炎(AH)组和乙醇性脂肪肝(AFL)组,结果显示AH 组TUNEL指数也较AFL组高(3．24±1．50％ vs 1．12± 0．63％,P<0．05),差异显著．结论:过量饮用乙醇可以引起中毒性肝脏疾病,饮用乙醇及持续时间与肝损伤的发生有密切关系．细胞凋亡在乙醇诱发肝损伤时可能起着重要作用．

AIM： To investigate the role of hepatocyte apoptosis in the pathogenesis of alcohol-induced liver diseases （ALD） in rats. METHODS： The rat model of liver injury was induced by combination of drinking and gastric irrigation of ethanol. The morphological changes of the liver were observed by routine HE staining under light microscope. The hepatocyte apoptosis was examined by TUNEL, and the levels of serum alanine aminotransferase （ALT） and aspartate transaminase （AST） were detected by the rate method. RESULTS： At the end of the 5th week, the light and moderate steatosis appeared in ethanol-treated rat livers, the proportion of fatty degeneration was 40% （8/20）; At the end of the 10th week, the proportion was increased to 85%（17/20）, and the morphologi- cal changes of alcoholic hepatitis （AH） were found in 45%（9/20） rats. The serum levels of ALT and AST （nkat/L） in ethanol-treated rats were significantly higher than those of the controls （5 wk： 1 017±267 vs 550±133, P 〈0.05; 1 350±333 vs 967±150, P 〈0.05; 10 wk： 1 500±267 vs 767±250, P 〈0.05; 2 167±533 vs 850± 183, P 〈0.05）, and ALT and AST levels at 10 wk were also higher than those at 5 wk （P 〈0.05）. The TUNEL indexes （%） at 5 and 10 wk were 0.33±0.49% and 2.03 ±1.61% respectively （P 〈0.05）, and the index at 10 wk was significantly different from that of the controls （0.10 ±0.21%, P 〈0.05）. Furthermore, the TUNEL index of alcoholic hepatitis was significantly higher than that of alcoholic fatty liver （3.24±1.50% vs 1.12±0.63%, P 〈0.05）. Both show the significant difference. CONCLUSION： Chronic and excessive ethanol consumption can cause liver injury in rats. The amount and time of daily ethanol intake is closely related with the degrees of liver injury. Hepatocyte apoptosis may play an important role in the pathogenesis of ALD.