Abstract

Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.

Highlights

  • It was found that hypothalamus Corticotropin-releasing factor (CRF), serum adrenocorticotropic hormone (ACTH) and CORT levels were increased in model group compared with the intact group, and those in the EA

  • Surgical trauma leads to dysfunction of the hypothalamic pituitary adrenal axis (HPA axis), and results in hypermetabolic, organ damage or immunosuppression [1] [2]

  • CRF is a peptide released by the hypothalamus, which is widely distributed in almost all brain regions, and plays a pivotal role in the endocrine, autonomic and behavioral responses to stress by interacting mostly with GABAergic neurons [14] [15]

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Summary

Introduction

Surgical trauma leads to dysfunction of the hypothalamic pituitary adrenal axis (HPA axis), and results in hypermetabolic, organ damage or immunosuppression [1] [2]. The anti-stress effects of EA were most likely derived from its capacity to decrease the levels of serum ACTH and Cortisol [12] and its ability to down-regulate CRF over-expression in the hypothalamus in rats undergoing surgery [13]. CRF is a peptide released by the hypothalamus, which is widely distributed in almost all brain regions, and plays a pivotal role in the endocrine, autonomic and behavioral responses to stress by interacting mostly with GABAergic neurons [14] [15]. Effects of EA on the regulation of inhibitory actions of GABAergic neurons to CRF in the hypothalamus need more understanding. Hypothalamus GABA receptors were taken into consideration of the regulation functions following EA intervention in trauma rats

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