Yokoyama H, Nagata S, Moriya S, Kato S, Ito T, Kamegaya K, Ishii H
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hepatology. 1995 May;21(5):1438-42.
Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.
在豚鼠身上制造了实验性肝纤维化。我们在用乙醛加合物免疫并喂食乙醇40天的豚鼠身上制造了伴有炎性细胞浸润的肝坏死。将这些处理的时间延长至90天导致在终末肝小静脉区域和门静脉区域的单个肝细胞周围出现肝纤维化，同时肝羟脯氨酸含量增加。相比之下，在未接受任何处理、仅接受乙醇处理或接受乙醇与未修饰的人血红蛋白免疫联合处理的对照组肝脏中未观察到纤维化。在用乙醛加合物修饰的人血红蛋白免疫但未喂食乙醇的动物中观察到最小程度的纤维化改变。这些结果表明乙醛加合物的形成以及针对它们的免疫获得可导致肝纤维化。针对乙醛加合物的免疫机制可能部分参与了酒精性肝病患者肝纤维化的发病过程。
