Secretagogin Mediates the Regulatory Effect of Electroacupuncture on Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Surgical Trauma.

Mizhen Zhang,Yu Wang,Jingxian Sun,Zhanzhuang Tian,Clive R Bramham

doi:10.1155/2021/8881136

Abstract

Electroacupuncture (EA) improves hypothalamic-pituitary-adrenal (HPA) axis disorder by reducing corticotropin-releasing hormone (CRH) synthesis and release in the paraventricular nucleus (PVN). However, the potential mechanism underlying CRH regulation remains unclear. Secretagogin (SCGN) is closely related to stress and is involved in regulating the release of CRH. We hypothesized that SCGN in the PVN might trigger the HPA system and be involved in EA-mediated modulation of HPA dysfunction caused by surgical trauma. Serum CRH and adrenocorticotropic hormone (ACTH) and plasma corticosterone (CORT) levels at 6 h and 24 h after hepatectomy were determined by radioimmunoassay. CRH and SCGN protein levels in the PVN were detected by western blot and immunofluorescence, and CRH and SCGN mRNA levels in the PVN were determined by means of real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Our studies showed that serum CRH, ACTH, and CORT levels and PVN CRH expression were significantly increased at 6 h and 24 h after hepatectomy in the hepatectomy group compared with the control group, and those in the EA+hepatectomy group were decreased compared with those in the hepatectomy group. The protein and mRNA levels of SCGN in the PVN were also increased after hepatectomy, and their expression in the EA+hepatectomy group was decreased compared with that in the hepatectomy group. When SCGN expression in the PVN was functionally knocked down by a constructed CsCI virus, we found that SCGN knockdown decreased the serum CRH, ACTH, and CORT levels in the SCGN shRNA+hepatectomy group compared with the hepatectomy group, and it also attenuated CRH expression in the PVN. In summary, our findings illustrated that EA normalized HPA axis dysfunction after surgical trauma by decreasing the transcription and synthesis of SCGN.

Highlights

Surgery can improve health conditions while bringing about a series of adverse consequences, such as endocrine dysfunction [1], inflammation [2], immunosuppression [3], depression [4], and loss of memory [5], even with the rapid development of surgical techniques
To identify the regulation of EA in the hepatectomy rats, we detected the level of the serum corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and CORT and found that at 6 h after hepatectomy, CRH, ACTH, and CORT levels were increased in the hepatectomy group in comparison with the control ones
At 6 h after operation, by comparing with the control group, the CRH protein level in paraventricular nucleus (PVN) was upregulated in the hepatectomy group, and in comparison with the hepatectomy group, CRH protein level was downregulated in the EA+hepatectomy group, but there was no statistical significance

Summary

Introduction

Surgery can improve health conditions while bringing about a series of adverse consequences, such as endocrine dysfunction [1], inflammation [2], immunosuppression [3], depression [4], and loss of memory [5], even with the rapid development of surgical techniques. A few treatments can relieve adverse reactions caused by surgery [6], it is still difficult to recover from the surgery-induced stress response. The hypothalamic-pituitary-adrenal (HPA) axis, a crucial component of the stress response [7], plays an important role in maintaining homeostasis, and the paraventricular nucleus (PVN) is the initial and central part of the HPA axis. Adrenocorticotropic hormone (ACTH) is released from the anterior lobe of the pituitary, which is triggered by CRH, and ACTH can stimulate the adrenal cortex to secrete. The mechanism of regulation of CRH synthesis and release in trauma is still obscure. It is necessary to investigate new targets for improving HPA axis dysfunction caused by surgical trauma

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Results

Conclusion