有氧运动通过调节海马小胶质细胞表型极化缓解青春期间歇性酒精暴露所致的成年期大鼠认知障碍

Aerobic exercise relieves adolescent intermittent ethanol exposure-induced cognitive impairment in adult rats by regulating microglial polarization in hippocampus

目的:探究有氧运动对青春期间歇性酒精暴露(AIE)大鼠成年期海马小胶质细胞活化水平和表型极化的影响。方法:出生后28 d(P28)的雄性Wistar大鼠随机分为生理盐水安静(SS)组、生理盐水运动(SE)组、酒精安静(AS)组和酒精运动(AE)组。从P28到P55,AS和AE组大鼠进行酒精灌胃(200 g/L乙醇,5.0 g/kg,2 d灌胃,2 d休息,共灌胃4周),SS和SE组大鼠在同一时点接受等体积的生理盐水灌胃。从P28到P83,SE和AE组大鼠进行8周跑台运动干预。八臂迷宫实验检测大鼠学习记忆能力;免疫荧光染色检测海马组织小胶质细胞数量、形态和表型;ELISA检测海马组织促炎因子和抗炎因子的表达。结果:运动减少AIE大鼠八臂迷宫实验中的工作记忆错误和完成时间(P<0.05或P<0.01)。运动减少AIE大鼠海马组织小胶质细胞数量(P<0.01),降低小胶质细胞形态指数(P<0.01)。运动减少AIE大鼠海马组织M1型小胶质细胞数量(P<0.01),增加M2型小胶质细胞数量(P<0.01)。运动减少AIE大鼠海马组织促炎因子白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α的释放(P<0.05或P<0.01),增加抗炎因子IL-10的释放(P<0.05)。结论:有氧运动可诱导海马小胶质细胞M2型极化增加,减少小胶质细胞激活,抑制神经炎症,这可能是运动改善青春期酒精滥用所致认知损伤的中枢机制之一。

AIM:To explore the effects of aerobic exercise on the activation and polarization of microglia in the hippocampus of adult rats with adolescent intermittent ethanol exposure(AIE). METHODS:Male Wistar rats on postnatal day 28(P28) were randomly divided into saline sedentary(SS), saline exercise(SE), alcohol sedentary(AS) and alcohol exercise(AE) groups. The rats in AS and AE groups were given ethanol gavage(200 g/L ethanol, 5. 0 g/kg) on a two-day-on and two-day-off schedule for 4 weeks, while the rats in SS and SE groups received comparable volumes of saline on the same schedule. The rats in SE and AE groups were introduced to a treadmill exercise. Eight-arm maze test was used to determine the learning and memory abilities. Immunofluorescence staining was used to detect the quantity, morphology and polarization of microglia in the hippocampus. The levels of pro-inflammatory mediators and anti-inflammatory mediator were detected by ELISA. RESULTS:Exercise decreased AIE-induced increments of working memory errors and finish time(P<0. 05 or P<0. 01). Exercise decreased AIE-induced the number and morphological index of microglia in the hippocampus(P<0. 01). Exercise decreased the number of M1 microglia and increased the number of M2microglia in the hippocampus of AIE rats(P<0. 01). Exercise decreased the levels of interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α and increased IL-10 level in the hippocampus(P<0. 05 or P<0. 01). CONCLUSION:Aerobic exercise stimulates M2 polarization of microglia, and decreases microglial activation and neuroinflammation in the hippocampus of AIE rats.