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

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.

electroacupuncture; intestine; microRNAs; neuroimmunomodulation; reperfusion injury.