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GLP-1对大鼠下丘脑室旁核神经分泌大细胞活动的影响机制

金鑫¹, 陈丽^2,3, 初春平², 李玉子¹, 任鹏⁴, 邱德来^2,*

¹延边大学附属医院(延边医院)心血管内科，延吉 133000；²吉林医药学院脑科学研究院，吉林 132013；³延边大学生理与病理生理学教研室，延吉 133002；⁴玉溪师范学院体育学院，玉溪 653100

摘要

脑内的胰高血糖素样肽-1 (glucagon-like peptide 1, GLP-1)由前胰高血糖素原神经元合成，并通过轴突投射释放到弓状核、下丘脑室旁核(paraventricular nucleus, PVN)、延髓头端腹外侧和背内侧等广泛区域，参与物质代谢、神经内分泌调节和自主神经调控等功能活动。GLP-1 受体在PVN中表达丰富，在应激反应和心血管活动中起重要作用，但GLP-1 对下丘脑PVN神经分泌大细胞(magnocellular neurosecretory cells, MNCs)活动的影响机制尚未明确。本研究采用急性下丘脑切片全细胞膜片钳记录、生物素染色、双重免疫荧光染色和神经药理学等技术手段，研究GLP-1 对大鼠下丘脑PVN MNCs活动调控作用机制。在电流钳下，灌流GLP-1 (100 nmol/L)导致PVN MNCs的自发性放电频率显著降低和膜电位超极化。单独或同时阻断促离子型谷氨酸受体和GABAA受体，不影响GLP-1 对PVN MNCs放电频率的抑制作用。GLP-1 对动作电位的半宽值、上升常数、衰退常数均没有明显影响，但可显著增加PVN MNCs的后超极化电位(after-hyperpolarization, AHP)和内向整流钾电流。双重免疫荧光结果显示，GLP-1 显著减少精氨酸加压素(arginine vasopressin, AVP)能神经元的c-fos 表达。上述结果表明，GLP-1 活化突触后内向整流钾通道，降低PVN MNCs兴奋性，减少其放电频率和c-fos 表达，提示GLP-1 通过抑制PVNMNCs的功能活动降低大鼠AVP的分泌和释放。

关键词： 胰高血糖素样肽-1; 脑片膜片钳记录; 下丘脑室旁核; 神经分泌大细胞; 内向整流钾电流

Effect of GLP-1 on MNCs activity in hypothalamic paraventricular nucleus in vitro in rats

JIN Xin¹, CHEN Li^2,3, CHU Chun-Ping², LI Yu-Zi¹, REN Peng⁴, QIU De-Lai^2,*

¹Department of Cardiology, Yanbian University Hospital, Yanji 133000, China；²Brain Science Institute, Jilin Medical University, Jilin 132013, China；³Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China；⁴College of Physical Education, Yuxi Normal University, Yuxi 653100, China

Abstract

Glucagon-like peptide-1 (GLP-1) in the brain is synthesized by preproglucagon neurons and released through axonal projections to extensive regions such as the arcuate nucleus, hypothalamic paraventricular nucleus (PVN), rostral ventrolateral medulla, and dorsomedial medulla. It is involved in functional activities including substance metabolism, neuroendocrine regulation, and autonomic nerve control. The GLP-1 receptor (GLP-1R) is highly expressed in the PVN and plays an important role in stress responses and cardiovascular activities. However, the mechanism by which GLP-1 influences the activity of magnocellular neurosecretory cells (MNCs) in the hypothalamic PVN remains unclear. In this study, we used whole-cell patch-clamp recording in acute hypothalamic slices, biotin staining, double immunofluorescence staining, and neuropharmacology methods to investigate the regulatory mechanism of GLP-1 on the activity of the hypothalamic PVN MNCs in vitro in rats. Under current-clamp conditions, perfusion with GLP-1 (100 nmol/L) resulted in a significant decrease in the spontaneous firing frequency of PVN MNCs accompanied with a membrane potential hyperpolarization. Blocking ionotropic glutamate receptors and GABAA receptors either alone or simultaneously did not affect the inhibitory effect of GLP-1 on the firing frequency of PVN MNCs. GLP-1 had no significant impact on the half-width, rise constant, or decay constant of action potentials, but it significantly increased the after-hyperpolarization (AHP) and inwardly rectifying potassium currents of PVN MNCs. The results of double immunofluorescence showed that GLP-1 significantly reduced the expression of c-fos in arginine vasopressin (AVP)-ergic neurons. These results indicate that GLP-1 activates postsynaptic inwardly rectifying potassium channels, reduces the excitability of PVN MNCs, and decreases their firing frequency and c-fos expression. These findings suggest that GLP-1 reduces the secretion and release of AVP by inhibiting the functional activity of PVN MNCs in rats.

Key words: glucagon-like peptide-1; brain slice patch-clamp recording; hypothalamic paraventricular nucleus; magnocellular neurosecretory cells; inwardly rectifying potassium currents

收稿日期：　　录用日期：

通讯作者：邱德来　　E-mail:

DOI: 10.13294/j.aps.2026.0042

引用本文：

金鑫, 陈丽, 初春平, 李玉子, 任鹏, 邱德来. GLP-1对大鼠下丘脑室旁核神经分泌大细胞活动的影响机制[J]. 生理学报 2026; 78 (3): 642-652.

JIN Xin, CHEN Li, CHU Chun-Ping, LI Yu-Zi, REN Peng, QIU De-Lai. Effect of GLP-1 on MNCs activity in hypothalamic paraventricular nucleus in vitro in rats. Acta Physiol Sin 2026; 78 (3): 642-652 (in Chinese with English abstract).