4.8 Article

Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus

期刊

THERANOSTICS
卷 11, 期 9, 页码 4078-4089

出版社

IVYSPRING INT PUBL
DOI: 10.7150/thno.52574

关键词

gastrointestinal motility; macrophages; alpha 7nAChR; JAK2/STAT3 signaling pathway; GABA(A) receptor

资金

  1. National Science Fund for Distinguished Young Scholars [81825024]
  2. National Key R&D Program of China [2019YFC1712100]

向作者/读者索取更多资源

The study investigated how electroacupuncture stimulation at the hindlimb region ameliorates inflammation in postoperative ileus (POI). Results showed that electroacupuncture suppressed intestinal inflammation and promoted gastrointestinal motility by activating the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR)-mediated JAK2/STAT3 signaling pathway in macrophages. Furthermore, hindlimb region stimulation inhibited the expression of GABA(A) receptor in dorsal motor nucleus of vagal (DMV) neurons, leading to suppression of inflammation via vagal efferent output.
Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of alpha 7nAChR antagonists (methyllycaconitine and alpha-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABA(A)) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABA(A) receptor) or muscimol (agonist of GABA(A) receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the alpha 7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABA(A) receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABA(A) receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of alpha 7nAChR-mediated JAK2/STAT3 signaling pathway.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据