课题基金基金详情
穿心莲内酯调控Nrf2通路及IL-23/IL-17轴治疗溃疡性结肠炎的作用机制研究
结题报告
批准号:
82004040
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
朱琴
依托单位:
学科分类:
中药消化与呼吸药理
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
朱琴
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中文摘要
溃疡性结肠炎(Ulcerative Colitis,UC)好发于青壮年,病程迁延复发,但目前治疗药物仍存在副作用多、耐药及价格昂贵的缺点,有必要研发具有自主知识产权的抗UC药物。UC发病机制仍未明确,目前认为肠上皮屏障受损(Nrf2通路)及免疫应答失常(IL-23/IL-17轴)在UC的发病中起到重要作用。我们前期研究已证实穿心莲内酯能够下调IL-23/IL-17轴,抑制肠道炎症,促进黏膜修复。进一步预实验发现Nrf2抑制剂可以阻断穿心莲内酯对IL-23/IL-17轴的下调,提示Nrf2通路能够调控IL-23/IL-17轴,穿心莲内酯可能通过激活Nrf2下调IL-23/IL-17轴。本项目拟构建Nrf2肠上皮特异性基因敲除小鼠及基因沉默细胞,基于Nrf2通路及IL-23/IL-17轴,进一步探讨UC发病分子机制、穿心莲内酯对UC肠上皮屏障及免疫应答的作用,以阐明其治疗UC的作用机制及靶点。
英文摘要
Ulcerative colitis (UC), a chronic, nonspecific intestinal inflammatory disease, usually occurs in young adults with high recurrence rate.Impaired intestinal epithelial barrier (Nrf2 pathway) and immune response (IL-23 / IL-17 axis) play important roles in the pathogenesis of UC. Our previous studies confirmed that andrographolide can down-regulate the IL-23 / IL-17 axis, inhibit intestinal inflammation, and promote mucosal repair. Our preliminary experiments found that Nrf2 inhibitors can block the down-regulation of andrographolide on the IL-23 / IL-17 axis, suggesting that andrographolide may down-regulate the IL-23 / IL-17 axis by activating the Nrf2 pathway. This project intends to construct Nrf2 epithelial-specific knockout mice and gene silencing cells. Based on the Nrf2 pathway and the IL-23 / IL-17 axis, to explore the effect of andrographolide on the intestinal epithelial barrier and immune response of UC, in order to clarify its mechanism and target.The result will provide clues and basis for clinical application of andrographolide in the treatment of UC.
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