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基于TNF-ɑ/Elk-1/MLCK信号通路探讨清热化湿法修复溃疡性结肠炎肠黏膜屏障损伤的作用机制

基于TNF-ɑ/Elk-1/MLCK信号通路探讨清热化湿法修复溃疡性结肠炎肠黏膜屏障损伤的作用机制
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  • 批准号:81673731
  • 批准年度: 2016年
  • 学科分类:中西医结合临床基础(H2902) |
  • 项目负责人:柯晓
  • 负责人职称:主任医师
  • 依托单位:福建中医药大学
  • 资助金额:60万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: TNF-ɑ/Elk-1/MLCK;清热化;溃疡性结肠炎;屏障;损伤
  • 英文关键词:Heat-Clearing and Dampness-Dissipating;Ulcerative colitis;TNF-ɑ/Elk-1/MLCK Signaling pathway; Intest

项目摘要

中文摘要

溃疡性结肠炎(UC)的发生发展与肠黏膜屏障破坏密切相关。TNF-ɑ/Elk-1/MLCK通路异常激活介导的细胞紧密连接破坏是肠黏膜屏障受损的重要调节机制之一。大肠湿热证为UC的主要证型,清热化湿法为重要治则。清化肠饮是名老中医杨春波经验方,主治大肠湿热型UC,治疗效果显著。课题组前一个国家自然科学基金项目研究表明清化肠饮可明显改善UC小鼠结肠黏膜的组织学损伤并显著降低LPS介导的肠上皮细胞TNF-ɑ的分泌,提示通过调控TNF-ɑ/Elk-1/MLCK通路、继而促进肠黏膜屏障修复可能是清化肠饮治疗UC的重要机制。在此基础上本课题拟通过体内外实验,采用检测跨膜电阻、糖分子探针等方法研究清化肠饮对UC结肠黏膜通透性的影响,并采用Q-PCR、Western-blot等方法研究清化肠饮对该通路活化和细胞紧密连接蛋白表达的影响。研究将助于进一步阐明清化肠饮治疗UC的内在机制,为其临床应用提供实验依据。

英文摘要

The damage of intestinal mucosal barrier is strongly associated with the development of ulcerative colitis (UC). The abnormal activation of TNF-ɑ/Elk-1/MLCK signal pathway has been implicated as a key mediator for the disturbance in the intestinal the disturbance in the intestinal TJ barrier, which contributed to the impaired intestinal mucosal barrier. Qing Hua Chang Yin (QHCY) is a traditional Chinese formula, which has been demonstrated to be clinically effective in the treatment of UC. However, the precise mechanisms behind its anti‑inflammatory effects remain largely unknown. Our previous studies showed that QHCY can ameliorate histologcal damage of intertstinal mucosa in DSS-induced UC mouse model and reduce the secretion of TNF-ɑ in LPS-stimulated differciated Caco-2 cells. Our findings suggest that QHCY treat UC could through reverse the damage of Intestinal mucosal barrier, which involving in TNF-ɑ/Elk-1/MLCK signal pathway. In the present project we will study the in vivo and in vitro effects of QHCY on the intestinal permeability by measurement of transepithelial electric resistance (TEER) and detection of sugar molecular probes. the Effect of QHCY on the activation of TNF-ɑ/Elk-1/MLCK pathway and the expression of cell tight junction protein will be explored by immunohistochemical staining, Western blot and Real-time quantitative RT-PCR. Our findings in this study will provide new insight into the molecular mechanism of the anti-inflammatory activity of QHCY in UC. It will provide further experimental evidence for clinically treatment of UC.

评估说明

    国家自然科学基金项目“基于TNF-ɑ/Elk-1/MLCK信号通路探讨清热化湿法修复溃疡性结肠炎肠黏膜屏障损伤的作用机制”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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