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首页> 外文期刊>Cellular Physiology and Biochemistry >Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models
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Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models

机译：伴刀豆球蛋白a诱导的小鼠自身免疫性肝炎模型的比较

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Background/Aims Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver whose pathogenic mechanisms have not yet been elucidated. Moreover, the current treatment used for the vast majority of AIH patients is largely dependent on immunosuppressant administration and liver transplantation. However, research on the pathogenesis of AIH and effective new treatments for AIH have been hampered by a lack of animal models that accurately reproduce the human condition. Methods AIH models created by concanavalin A (ConA) injections at different times and doses. The levels of ALT, AST, LDH and inflammatory cytokines were examined at various times after 20 mg/kg ConA was administered by ELISA using commercially available kits. Moreover, liver pathological changes were observed by flow cytometry (FCM) and H&E staining. Results Our experiments demonstrated that the levels of ALT, AST, LDH and several inflammatory cytokines, including TNF-α, IFN-γ, and IL-6, were higher in the 20 mg/kg 12 h ConA group than in the other groups. Importantly, the numbers of activated CD4+ and CD8+ T lymphocytes in the blood, spleen and liver were calculated. These results showed that ConA (20 mg/kg for 12 h)-induced hepatitis was similar to that in clinical AIH patients. Furthermore, we found that the number of MDSCs in the blood was significantly increased in the ConA (20 mg/kg for 12 h) group compared with controls. Our findings indicated that ConA (20 mg/kg for 12 h)-induced hepatitis could be used as an experimental murine model that mirrors most of the pathogenic properties of human type I AIH. Conclusion This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.
机译：背景/目的自身免疫性肝炎（AIH）是一种慢性肝炎性炎症，其致病机制尚未阐明。此外，目前用于绝大多数AIH患者的治疗很大程度上取决于免疫抑制剂的给药和肝移植。但是，由于缺乏能够精确复制人类状况的动物模型，阻碍了AIH发病机理的研究和AIH的有效新治疗方法。方法通过不同时间和剂量注射刀豆球蛋白A（ConA）创建的AIH模型。使用市售试剂盒通过ELISA施用20 mg / kg ConA后，在不同时间检查ALT，AST，LDH和炎性细胞因子的水平。此外，通过流式细胞术（FCM）和H＆＃38染色观察到肝脏病理变化。结果我们的实验表明，在20 mg / kg 12 h ConA组中，ALT，AST，LDH和几种炎症细胞因子（包括TNF-α，IFN-γ和IL-6）的水平高于其他组。重要的是，计算了血液，脾脏和肝脏中活化的CD4 +和CD8 + T淋巴细胞的数量。这些结果表明，ConA（20 mg / kg，持续12 h）诱发的肝炎与临床AIH患者相似。此外，我们发现，与对照组相比，ConA组（20 mg / kg，持续12 h）血液中MDSC的数量显着增加。我们的发现表明，ConA（20 mg / kg，持续12 h）诱发的肝炎可以用作实验性小鼠模型，该模型反映了人类I型AIH的大部分致病特性。结论该模型[ConA（20 mg / kg持续12 h）]为研究AIH免疫发病机制和快速评估新的治疗方法提供了有价值的工具。

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