Electroacupuncture at Zusanli (ST36) Alleviate Intestinal Ischemia‐Reperfusion Injury by Regulating the Cholinergic‐miRNA 124 Pathway

ABSTRACT Objective Intestinal ischemia‐reperfusion injury (IIRI) is common in a variety of critical diseases and acute stress, and acupuncture is a promising treatment for IIRI. The aim of this study is to explore the mechanism of electroacupuncture (EA) at Zusanli (ST36) in improving IIRI from the perspective of the cholinergic anti‐inflammatory pathway (CAP) and miRNA 124. Methods Seven groups of mice were performed: Control group, I/R group (IIRI model), EA group (I/R + EA), miRNA mimic group (I/R + EA + miRNA 124 mimic), miRNA inhibitor group (I/R + EA + miRNA 124 inhibitor), PNU group (I/R + EA + α7nAChR agonist), and MLA group (I/R + EA+ α7nAChR antagonist). The expression of intestinal macrophages, α7nAChR, miRNA 124, and related molecules, including p‐STAT3 and IL‐6, as well as histological damage (Chiu's score) and mucosal permeability (serum FD4 concentration), were detected. Results The serum FD4 concentrations in the EA and PNU groups were significantly lower compared to the I/R group ( p < 0.05). The expression of intestinal α7nAChR and miRNA 124 in the EA, miRNA mimic, and PNU groups was higher than that in the I/R group ( p < 0.05), while levels of p‐STAT3 and IL‐6 were reduced ( p < 0.05). Conversely, in the miRNA inhibitor and MLA groups, miRNA 124 levels were significantly lower than in the EA group ( p < 0.05), and IL‐6 levels were increased ( p < 0.05). Conclusion EA at Zusanli may induce miRNA124 through the cholinergic pathway on intestinal macrophages, which may be a key neuro‐immune target of EA in the treatment of IIRI.