Electroacupuncture Alleviates Surgical Trauma-Induced Hypothalamus Pituitary Adrenal Axis Hyperactivity Via microRNA-142.

Jing Zhu,Haidong Guo,Zhanzhuang Tian,Gencheng Wu,Minda Ju,Zhejun Chen,Zehui Meng,Mizhen Zhang

doi:10.3389/fnmol.2017.00308

Abstract

Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying mechanism still remains largely unclear. Here, we found that hypothalamic corticotrophin releasing hormone (CRH) modulates the function of the HPA axis, while hepatectomy induced an HPA axis disorder and EA application could regulate the hypothalamic CRH. We first demonstrated that microRNAs (miRNAs) target on CRH via bioinformatics analysis and screened them in the primary hypothalamic neurons. MicroR-142 (miR-142) and miR-376c were identified to inhibit CRH at the mRNA and protein levels, and a dual luciferase reporter assay confirmed their binding to the 3′-untranslated regions (3′-UTR) of CRH. Further analyses revealed a decrease in hypothalamic miR-142 expression in the hepatectomy rats and an increase in miR-142 and miR-376c after EA intervention. Importantly, the improvement effect of EA on the HPA axis regulatory function in hepatectomy rats was blocked by miR-142 antagomir. Our findings illustrated that EA could up-regulate hypothalamic miR-142 expression and decrease the CRH level to alleviate the hyperactivity of the HPA axis induced by hepatectomy.

Highlights

Surgery or severe trauma induces the dysfunction of the neurogenic, immune and endocrine systems (Aller et al, 2013), resulting in immunosuppression, aprosexia and other stress reactions (Morrison et al, 1996), always with a poor prognosis
EA Attenuated the hypothalamus pituitary adrenal (HPA) Axis Hyperactivity Induced by Hepatectomy
The positive miRNA expression of paraventricular nucleus (PVN) was detected under an optical microscope

Summary

Introduction

Surgery or severe trauma induces the dysfunction of the neurogenic, immune and endocrine systems (Aller et al, 2013), resulting in immunosuppression, aprosexia and other stress reactions (Morrison et al, 1996), always with a poor prognosis. Some treatments have contributed to improving these reactions (Marik and Flemmer, 2012), it is still hard to rectify trauma-induced homeostasis disorder. The hypothalamus pituitary adrenal (HPA) axis plays an inevitable role in controlling the stress reaction, especially those induced by surgery and severe injury (Gibbison et al, 2013). The paraventricular nucleus (PVN) in the hypothalamus, adenohypophysis and the cortex of the adrenal glands contribute to the HPA axis. There is surprisingly little known about the role of hypothalamic CRH in severe injury or surgical trauma. The neural mechanism by which surgery produces HPA axis disorder is unclear

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