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

原发性胆汁性肝硬化动物模型的开发及其发病机制的阐明

• 批准号: 02670306
• 负责人: YAMAMOTO Kazuhide
• 金额: $ 1.54万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670306/
• 关键词: THYMECTOMIZED MICE; PRIMARY BILIARY CIRRHOSIS; ANTI-MITOCHONDORIAL ANTIBODY; 慢性非化膿性破壊性胆管炎; 胆管上皮抗原

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.

为探讨原发性胆汁性肝硬化（PBC）的发病机制，制备了PBC动物模型，并进行了形态学和免疫学分析。用来自猪肝的各种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。病变伴有单核细胞密集浸润及胆管上皮细胞变性。单核细胞由淋巴细胞、浆细胞和巨噬细胞组成。胆管周围可见CD4+和CD8+淋巴细胞，以CD4+淋巴细胞为主。MHC I类和II类抗原均在胆管上皮细胞上表达。血清学上，存在抗线粒体抗体，并显示为丙酮酸脱氢酶抗体，与人PBC相同。此外，在血清中显示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表现类似于人PBC，可以用作PBC的动物模型。需要进一步的研究来评估动物模型。

项目成果

Yamamoto K, et al: "Ultrastructural observation of bile duct lesions in an experimental model of primary biliary cirrhosis." J Clin Electron Microscopy. 24. 620-621 (1991)

Yamamoto K 等人：“原发性胆汁性肝硬化实验模型中胆管病变的超微结构观察。”

Yamamoto K,et al.: "Ultrastructural observation of bile duct lesions in an experimental model of primary leiliary cirrhosis." J.Clin Electron Microscopy. 24. 620-621 (1991)

Yamamoto K 等人：“原发性杂状肝硬化实验模型中胆管病变的超微结构观察。”

YAMAMOTO K,et al: "Ultrastructural observation of lrile duct lesions in an experimental model of primary biliary cirshosis" J.Clin Electron Microscopy. 24. 620-621 (1991)

YAMAMOTO K 等人：“原发性胆汁性肝病实验模型中输卵管病变的超微结构观察”J.Clin 电子显微镜。

Kobashi H, et al: "An experimental animal model for primary biliary cirrhosis using neonatally thymectomized mice. (in Japanese)" Kanzo. 32. 965 (1991)

Kobashi H 等人：“使用新生胸腺切除小鼠建立原发性胆汁性肝硬化实验动物模型。（日语）”Kanzo。

小橋 春彦他: "新生期胸腺摘出マウスを用いた原発性胆汁性肝硬変(PBC)の動物実験モデル作成の試み" 肝臓. 32. 965 (1991)

Haruhiko Kobashi 等人：“尝试使用新生胸腺切除小鼠创建原发性胆汁性肝硬化 (PBC) 动物实验模型”Liver. 32. 965 (1991)