Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models
Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models
复制标题
刀豆球蛋白 a 诱导的小鼠自身免疫性肝炎模型的比较
DOI：
10.1159/000489074
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发表时间：
2018-04
影响因子：
--
通讯作者：
Yang Li
中科院分区：
文献类型：
--
作者：
Ye Tinghong;Wang Tingting;Yang Xiaoxue;Fan Xiaoli;Wen Maoyao;Shen Yi;Xi Xiaotan;Men Ruoting;Yang Li
背景/目的：自身免疫性肝炎（AIH）是一种慢性肝脏坏死性炎症性疾病，其发病机制尚未阐明。此外，目前用于绝大多数AIH患者的治疗在很大程度上依赖于免疫抑制剂和肝移植。然而，由于缺乏准确再现人类病情的动物模型，对AIH发病机制和有效的AIH新疗法的研究一直受到阻碍。方法：不同时间、不同剂量注射ConA建立AIH模型。采用市售试剂盒，用酶联免疫吸附法检测20 mg/kg ConA给药后不同时间的ALT、AST、LDH及炎症因子水平。流式细胞术（FCM）和H&E染色观察肝脏病理变化。结果：我们的实验表明，在20 mg/kg 12 h的ConA组中，ALT、AST、LDH和TNF-α、IFN-γ、IL-6等几种炎症细胞因子的水平高于其他组。重要的是，计算血液、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）诱导的肝炎与临床AIH患者相似。此外，我们发现，与对照组相比，ConA （20 mg/kg，持续12小时）组血液中MDSCs的数量显著增加。我们的研究结果表明，ConA （20 mg/kg持续12 h）诱导的肝炎可以作为一种反映人类I型AIH大部分致病特性的实验性小鼠模型。结论：该模型[ConA (20 mg/kg, 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。
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.
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Tim-3/galectin-9 通路参与刀豆球蛋白 A 诱导的肝炎小鼠模型中肝脏 Tregs 的稳态。
影响因子：
3.6
作者：
Ju, Ying;Shang, Xuming;Zou, Jianwen
通讯作者：
Zou, Jianwen
DOI：
--
发表时间：
1992-04
期刊：
Behring Institute Mitteilungen
影响因子：
--
作者：
K. M. Z. Büschenfelde;T. Poralla
通讯作者：
K. M. Z. Büschenfelde;T. Poralla
影响因子：
--
作者：
Xue, Jihua;Chen, Feng;Chen, Zhi
通讯作者：
Chen, Zhi
影响因子：
2.7
作者：
D. Villalta;E. Girolami;M. Alessio;M. C. Sorrentino;M. Tampoia;I. Brusca;M. Daves;B. Porcelli;G. Barberio;M. Conte;L. Pantarotto;N. Bizzaro
通讯作者：
D. Villalta;E. Girolami;M. Alessio;M. C. Sorrentino;M. Tampoia;I. Brusca;M. Daves;B. Porcelli;G. Barberio;M. Conte;L. Pantarotto;N. Bizzaro
影响因子：
7.7
作者：
P. Zaccone;J. Phillips;I. Conget;R. Gomis;K. Haskins;A. Minty;K. Bendtzen;A. Cooke;F. Nicoletti
通讯作者：
P. Zaccone;J. Phillips;I. Conget;R. Gomis;K. Haskins;A. Minty;K. Bendtzen;A. Cooke;F. Nicoletti