Pathogenesis of spontaneous hepatitis in LEC rats with combined immunodeficiency

联合免疫缺陷LEC大鼠自发性肝炎的发病机制

• 批准号: 61570163
• 负责人: TAKEICHI Noritoshi
• 金额: $ 1.54万
• 依托单位: Hokkaido 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: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570163/
• 关键词: LEC rats; Spontaneous hepatitis; Combined immunodificieney; Immunoglobulin; マクロファージ; 肝炎モデル動物; 劇症肝炎; 肝癌

We investigated LEC rats which spontaneously develop hepatitis to findout the cause immunopathologically, in comparison with non hepatitis LEA rats.Wet weight of spleen and thymus of 6-week old LEC rats was significantly lighter then that of LEA rat of the same age.Serum IgG level in LEC rats remained markedly low after the age of 4 weeks, and IgG antibody form ation to SRBC as detected by plaque assay was also significantly suppressed. Furthermore, genetic studies of crossing hybrids of LEA and LEC rats revealed that there was a close correlation between development of hepatitis and lower levels of IgG: no hepatitis case was found in F_1 group which had relatively high IgG levels, but many in F_2 and backcross groups which had lower IgG levels. On the other hand, IgG and IgM antibody formation was suppressed, though serum IgM level was normal or rather increased.Blastgenic response of spleen cells to PHA and Con A was much more suppressed in LEC rats than in LEA rats.Cytostatic activity of intraperitoneal macrophage against tumor cells was more evident inLEC rats than in LEA rats, but there was no difference inNK activity between the two rat strains. From these results, it is speculated that spontaneously hepatitisdeveloping LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activitiesare linked to the cause of developing hepatitis.

以自发性LEC大鼠为研究对象，通过与非肝炎大鼠的比较，探讨自发性LEC大鼠发生肝炎的免疫病理原因。6周龄LEC大鼠脾、胸腺湿重明显轻于同龄LEA大鼠。4周后，LEC大鼠血清IgG水平保持在较低水平，斑块法检测的SRBC IgG抗体形成也明显受到抑制。此外，对LEA和LEC杂交大鼠的遗传研究表明，肝炎的发生与IgG水平较低密切相关：IgG水平较高的F_1组未发现肝炎病例，而IgG水平较低的F_2和回交组有许多肝炎病例。另一方面，血清IgM水平正常或升高，但IgG和IgM抗体的形成受到抑制。脾细胞对PHA和Con A的成母反应在LEC大鼠中明显低于LEA大鼠。腹腔巨噬细胞对肿瘤细胞的抑制活性在lec大鼠比LEA大鼠更明显，但两大鼠之间的inkk活性无差异。根据这些结果，推测自发性肝炎LEC大鼠具有T和B细胞缺乏症（联合免疫缺陷），巨噬细胞和NK细胞活性的增加与肝炎发生的原因有关。

项目成果

武市紀年他: 医学の歩み. 136. 379-380 (1986)

Noritoshi Takeichi 等人：医学史 136. 379-380 (1986)

Takeichi,N.et al: Gastroenterology.(1988)

Takeichi,N.等人：胃肠病学。(1988)

Namieo, T. et al.: "Establishment of LEC (Long Evans Cinnamon) rats with spontaneous hepatitis." Journal of Japan Surgical Society.in press. (1988)

Namieo, T. 等人：“建立患有自发性肝炎的 LEC（长埃文斯肉桂）大鼠。”

Takeichi, N. et al.: "Combined innumodeficiency in LEC rats with spontaneous fulminant hepatitis." Igaku no ayumi (in japanese). 136. 379-380 (1986)

Takeichi, N. 等人：“患有自发性暴发性肝炎的 LEC 大鼠的联合免疫缺陷。”

Namieno, T. et al.: "Etiology for combined immunodeficiency in LEC rats with spontaneous hepatitis and hepatoma." Byotaiseiri (in japanese). 6. 385-386 (1987)

Namieno, T. 等人：“患有自发性肝炎和肝癌的 LEC 大鼠联合免疫缺陷的病因。”