Zhu Jing, Chen Zhejun, Meng Zehui, Ju Minda, Zhang Mizhen, Wu Gencheng, Guo Haidong, Tian Zhanzhuang
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Mol Neurosci. 2017 Sep 27;10:308. doi: 10.3389/fnmol.2017.00308. eCollection 2017.
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.
电针(EA)可改善肝切除术诱导的下丘脑-垂体-肾上腺(HPA)轴功能亢进。然而,其潜在机制仍不清楚。在此,我们发现下丘脑促肾上腺皮质激素释放激素(CRH)调节HPA轴功能,而肝切除术诱导HPA轴紊乱,电针治疗可调节下丘脑CRH。我们首先通过生物信息学分析证明微小RNA(miRNA)靶向CRH,并在原代下丘脑神经元中进行筛选。鉴定出MicroR-142(miR-142)和miR-376c在mRNA和蛋白质水平抑制CRH,双荧光素酶报告基因检测证实它们与CRH的3'非翻译区(3'-UTR)结合。进一步分析显示,肝切除大鼠下丘脑miR-142表达降低,电针干预后miR-142和miR-376c表达增加。重要的是,miR-142拮抗剂可阻断电针对肝切除大鼠HPA轴调节功能的改善作用。我们的研究结果表明,电针可上调下丘脑miR-142表达,降低CRH水平,从而减轻肝切除术诱导的HPA轴功能亢进。