有氧运动对慢性应激大鼠脑海马区神经可塑性的影响
Effects of Exercise on Neural Plasticity in Hippocampus of Rats with Chronic Stress

摘要：目的：以神经元和神经胶质细胞相关神经生物学变化为切入点，探讨有氧运动对慢性应激大鼠脑海马区神经可塑性的影响。方法：以SD大鼠为研究对象，按照体重均衡分为对照组（CON）、慢性应激模型组（MOD）、氟西汀组（FLU）、低强度运动组（LIR）和中等强度运动组（MIR）。给予大鼠4周慢性应激，并分别伴随氟西汀给药、低强度或者中等强度的运动干预。4周后，通过开场实验、蔗糖饮水实验、新奇抑制摄食实验以及新物体识别实验检测运动对慢性应激大鼠抑郁样行为、焦虑样行为以及认知障碍的影响；同时，利用酶联免疫法和蛋白免疫印迹法，检测运动对慢性应激大鼠血清皮质酮、海马内前炎因子IL1-β，以及蛋白GFAP、S100β、BDNF、p-ERK、p-CREB表达的影响，探讨运动抗抑郁的行为学效应和作用机制。结果：1）低强度和中等强度运动能够显著增加慢性应激大鼠的开场活动、缩短新奇抑制摄食潜伏期，同时提高慢性应激大鼠新物体的识别指数；2）运动有效逆转了慢性应激大鼠血清皮质酮的异常升高，同时降低海马内前炎性因子IL1-β的分泌；3）运动可显著星形胶质细胞的标志性功能蛋白GFAP和S100β的表达水平，增强慢性应激大鼠的BDNF/ERK/CREB信号转导通路中重要蛋白BDNF、p-ERK、p-CREB的表达。结论：运动可以通过提高慢性应激大鼠脑海马区神经可塑性来达到抗抑郁的目的。可能与以下因素有关：1）运动调节血清皮质酮的异常升高，降低海马内前炎性因子的释放，同时，提高与神经胶质细胞相关蛋白GFAP和S100β活性，从而起到神经元保护的作用；2）运动可以通过激活CREB，BDNF以及ERK等重要信号蛋白的表达，提高神经营养作用，促进神经元的生长，增加神经可塑性和神经发生来发挥抗抑郁作用。
Abstract: Purpose: The purpose of this study was to investigate the effects of aerobic exercise on neural plasticity in hippocampus of rats with chronic stress by analyzing the neurobiological changes of neurons and glial cells. Methods: Fifty male Sprague-Dawley rats were randomly divided into five groups, including control group (CON), chronic stress model group (MOD), CUS + fluoxetine group (FLU), CUS + low intensity running group (LIR) and CUS + moderate intensity running group (MIR). Rats were suffered 4 weeks chronic stress with FLU, low intensity exercise or moderate intensity exercise. The effects of exercise on depression-like behavior, anxiety-like behavior and cognitive impairment were tested by open field test (OFT), sucrose preference test (SP), novelty-suppressed feeding test (NSF) and novel object recognition experiment (NOR). The effects of exercise on serum corticosterone, inflammatory factors IL-1β, levels of GFAP, S100β, p-ERK, p-CREB and BDNF in hippocampus were tested by ELISA and Western blotting. These tests were for exploring behavioral effects and mechanisms of exercise’s anti-depression. Results: 1) Low intensity exercise and moderate intensity exercise increased the open activities, shorts latent period of novelty-suppressed feeding, and improve recognition index of novel object in rats with chronic stress. 2) Exercise effectively reversed the abnormal increase of serum corticosterone and decreased the secretion of IL-1β in the hippocampus of rats with chronic stress. 3) Exercise decreased the expressions of GFAP and S100β, and increased the expressions of BDNF, p-ERK and p-CREB that are important in BDNF/ERK/CREB signal transduction pathway in rats with chronic stress. Conclusions: Exercise can regulate the abnormal increase of serum corticosterone, reduce the release of inflammatory