EXPLOITATION OF AN ANIMAL MODEL FOR PRIMARY BILIARY CIRRHOSIS AND ELUCIDATION OF ITS PATHOGENESIS

为了阐明原发性胆汁性肝硬变(PBC)的发病机制，建立了PBC动物模型，并对其进行了形态学和免疫学分析。用猪肝胆汁抗原免疫新生胸腺切除(NTX)小鼠。胆管病变只出现在胆管抗原免疫的小鼠身上。病变伴有密集的单核细胞浸润和胆管上皮细胞变性。单个核细胞由淋巴细胞、浆细胞和巨噬细胞组成。胆管周围可见CD_4、CD_8淋巴细胞，以CD_4淋巴细胞为主。胆管上皮细胞表达MHC I类和II类抗原。在血清学上，存在抗线粒体抗体，并被证实是丙酮酸脱氢酶的抗体，与人的PBC一样。此外，在血清中还发现了几种针对免疫胆管抗原的抗体。这些结果表明，本模型的病理和免疫学结果与人的PBC相似，可以作为PBC的动物模型。还需要进一步的研究来评估该动物模型。

In order to elucidate the pathogenesis of primary biliary cirrhosis (PBC), an animal model for PBC was prepared and analyzed morphologically and immunologically. Neonatally thymectomized (NTx) mice were immunized with various biliary antigens from the porcine liver. Bile duct lesions appeared only in mice immunized with bile duct antigens. The lesions were accompanied by dense infiltration of mononuclear cells with degeneration of biliary epithelial cells. Mononuclear cells were composed of lymphocytes, plasma cells and macrophages. Both CD4+ AND CD8+ lymphocytes were observed around the bile duct and CD4+ lymphocytes were predominant. Both MHC class I and class II antigens were demonstrated on bile duct epithelial cells. Serologically, anti-mitochondrial antibody was present and was revealed to be the antibody to pyruvate dehydrogenase as in human PBC. Furthermore, several antibodies to immunized bile duct antigens were demonstrated in the serum. These results suggest that the pathological and immunological findings of the present model resembles human PBC and can be used as an animal model for PBC. Further studies are needed to evaluate the animal model.