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JAK2 抑制剂 AG490 调节 Treg/Th17 平衡,减轻 IBD 大鼠的 DSS 诱导的肠道损伤。

The JAK2 inhibitor AG490 regulates the Treg/Th17 balance and alleviates DSS-induced intestinal damage in IBD rats.

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Neonatology, The First People's Hospital of Lianyungang/The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China.

出版信息

Clin Exp Pharmacol Physiol. 2020 Aug;47(8):1374-1381. doi: 10.1111/1440-1681.13311. Epub 2020 May 11.

Abstract

The pathogenesis of inflammatory bowel disease (IBD) remains unclear, and it is currently believed that an imbalance in regulatory T (Treg) cells/T helper 17 cells (Th17 cells) is related to the occurrence and development of IBD. Recently, the JAK2 inhibitor AG490 has been used in animal models such as rheumatoid arthritis and bronchial asthma models and shown to exert immunoregulatory functions that improve disorder in the Treg/Th17 cell balance. This study aimed to evaluate the effect of AG490 on the intestinal inflammatory process in an IBD rat model. A dextran sulfate sodium (DSS)-induced IBD rat model was established, and disease activity index (DAI) scores were calculated. The histopathological damage score was determined by haematoxylin-eosin (H&E) staining. Treg/Th17 cells in the spleen were detected by flow cytometry. The levels of interleukin (IL)-10, IL-6 and IL-17A were detected by enzyme-linked immunosorbent assay (ELISA). AG490 attenuated DSS-induced IBD injury by regulating the Treg/Th17 balance and related cytokine secretion to reduce the DAI and colonic tissue damage. Thus, AG490 may be a new method for effective treatment of IBD.

摘要

炎症性肠病(IBD)的发病机制尚不清楚,目前认为调节性 T(Treg)细胞/辅助性 17 细胞(Th17 细胞)失衡与 IBD 的发生发展有关。最近,JAK2 抑制剂 AG490 已在类风湿关节炎和支气管哮喘模型等动物模型中得到应用,显示出免疫调节功能,可改善 Treg/Th17 细胞平衡紊乱。本研究旨在评估 AG490 对 IBD 大鼠模型肠道炎症过程的影响。建立葡聚糖硫酸钠(DSS)诱导的 IBD 大鼠模型,并计算疾病活动指数(DAI)评分。苏木精-伊红(H&E)染色法测定组织病理学损伤评分。流式细胞术检测脾内 Treg/Th17 细胞。酶联免疫吸附试验(ELISA)检测白细胞介素(IL)-10、IL-6 和 IL-17A 的水平。AG490 通过调节 Treg/Th17 平衡和相关细胞因子分泌来减轻 DAI 和结肠组织损伤,从而减轻 DSS 诱导的 IBD 损伤。因此,AG490 可能是治疗 IBD 的一种新方法。

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