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自主跑轮运动通过STAT3信号调控海马小胶质细胞极化抑制慢性应激所致大鼠抑郁样行为

罗婕¹, 王京琼¹, 谢丽娜¹, 孟安娜², 郑思思², 周寿红^2,3,*

¹湖南第一师范学院体育学院，长沙 410205；²广西脑与认知神经科学重点实验室，桂林 541199；³桂林医学院基础医学院生理学教研室，桂林 541199

摘要

本文旨在观察自主跑轮运动对慢性浸水束缚应激(chronic water immersion restraint stress, CWIRS)所致的大鼠抑郁样行为的作用及可能机制。用CWIRS诱导Sprague-Dawley (SD)大鼠产生抑郁样行为，给予大鼠4周自主跑轮运动干预，同时在大鼠侧脑室注射脂多糖(lipopolysaccharide, LPS)或STAT3过表达载体(pcDNA-STAT3)。用行为学实验检测大鼠抑郁样行为，用ELISA检测大鼠海马组织中多种炎症因子水平，用Western blot检测大鼠海马组织中离子钙结合接头分子1 (ionized calcium binding adaptor molecule 1, Iba1)、诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)、精氨酸酶1 (arginase 1, Arg1)、磷酸化STAT3 (p-STAT3)和总STAT3 (t-STAT3)蛋白表达水平。结果显示，与应激组相比较，应激+运动组大鼠抑郁样行为显著改善，海马组织中白细胞介素-1β (interleukin-1β, IL-1β)和IL-6水平显著降低，IL-4和IL-10水平显著升高，Iba-1和iNOS的蛋白表达水平显著下调，Arg1蛋白表达水平显著上调，p-STAT3/t-STAT3比值显著降低。LPS可逆转自主跑轮运动改善大鼠抑郁样行为的作用，过表达STAT3可逆转自主跑轮运动促进大鼠海马中小胶质细胞M2极化及改善大鼠抑郁样行为的作用。以上结果提示，自主跑轮运动可改善CWIRS诱导的大鼠抑郁样行为，其机制可能与自主跑轮运动通过STAT3信号途径调控海马小胶质细胞极化有关。

关键词： 自主跑轮运动; 慢性浸水束缚应激; 抑郁样行为; 海马; 小胶质细胞极化; STAT3

Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats

LUO Jie¹, WANG Jing-Qiong¹, XIE Li-Na¹, MENG An-Na², ZHENG Si-Si², ZHOU Shou-Hong^2,3,*

¹College of Physical Education, Hunan First Normal College, Changsha 410205, China；²Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin 541199, China；³Department of Physiology, Basic Medical College, Guilin Medical University, Guilin 541199, China

Abstract

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1β (IL-1β) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.

Key words: voluntary wheel running exercise; chronic water immersion restraint stress; depression-like behavior; hippocampus; microglia polarization; STAT3

收稿日期：　　录用日期：

通讯作者：周寿红　　E-mail: zhoushouhong@126.com

DOI: 10.13294/j.aps.2022.0029

引用本文：

罗婕, 王京琼, 谢丽娜, 孟安娜, 郑思思, 周寿红. 自主跑轮运动通过STAT3信号调控海马小胶质细胞极化抑制慢性应激所致大鼠抑郁样行为[J]. 生理学报 2022; 74 (2): 177-187.

LUO Jie, WANG Jing-Qiong, XIE Li-Na, MENG An-Na, ZHENG Si-Si, ZHOU Shou-Hong. Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats. Acta Physiol Sin 2022; 74 (2): 177-187 (in Chinese with English abstract).