Electroacupuncture alleviates perioperative hypothalamus-pituitary-adrenal axis dysfunction via circRNA-miRNA-mRNA networks.

Electroacupuncture (EA) has long been used to alleviate surgery-induced hypothalamic-pituitary-adrenal axis dysfunction. However, its downstream gene targets in the brain remain unclear. The aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were divided into normal control (NC), hepatectomy surgery (HT), HT + EA, and HT + sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala. Weighted Gene Co-expression Network Analysis and Gene Set Enrichment Analysis identified six gene modules associated with neuroendocrine transmitters and neural remodeling in the hypothalamus. Furthermore, circRNA-miRNA-mRNA interaction networks revealed EA-related candidate miRNAs and circRNAs, of which opioid receptor mu 1 might be an EA-specific target, and showed regulation by competing endogenous RNA. We identified the neuroendocrine circRNA-miRNA-mRNA networks through which EA has an effect on HPA axis dysfunction, thus providing potential targets and future research directions for EA treatment.