Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin.

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin.
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DOI:
10.3791/60067
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发表时间:
2019-09
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
通讯作者:
Ramkumar Mathur;Mahabub Alam;Xiao-Feng Zhao;Yunfei Huang;X. Zhu
Ramkumar Mathur;Mahabub Alam;Xiao-Feng Zhao;Yunfei Huang;X. Zhu
中科院分区:
其他
文献类型:
--
作者:
Ramkumar Mathur;Mahabub Alam;Xiao-Feng Zhao;Yunfei Huang;X. Zhu

文献摘要

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已经进行了重要的研究,以了解肠道纤维化的有效管理。然而,缺乏对纤维化的更好了解阻碍了预防药物的开发。首先,寻找合适的动物模型是理解克罗恩病相关肠纤维化病理机制的挑战。在这里,我们采用了一种有效的方法,其中TNBS化学品暴露于小鼠直肠产生实质性的深度溃疡和慢性炎症,然后小鼠慢性发展肠纤维化。此外,我们描述了一种技术,其中雷帕霉素注射显示对小鼠模型中TNBS介导的纤维化的抑制作用。为了评估纤维化的潜在机制,我们系统地讨论了从TNBS处理的小鼠和对照小鼠的固有层纯化Cx3Cr1+细胞的程序。这一详细的方案将有助于研究纤维化机制的研究人员,并为克罗恩病相关肠纤维化找到更好的治疗发明铺平道路。
Significant studies have been carried out to understand effective management of intestinal fibrosis. However, the lack of better knowledge of fibrosis has hindered the development of a preventative drug. Primarily, finding a suitable animal model is challenging in understanding the mechanism of Crohn's-associated intestinal fibrosis pathology. Here, we adopted an effective method where TNBS chemical exposure to mice rectums produces substantially deep ulceration and chronic inflammation, and the mice then chronically develop intestinal fibrosis. Also, we describe a technique where a rapamycin injection shows inhibitory effects on TNBS-mediated fibrosis in the mouse model. To assess the underlying mechanism of fibrosis, we methodically discuss a procedure for purifying Cx3Cr1+ cells from the lamina propria of TNBS-treated and control mice. This detailed protocol will be helpful to researchers who are investigating the mechanism of fibrosis and pave the path to find a better therapeutic invention for Crohn's-associated intestinal fibrosis.