游泳训练对脑出血大鼠认知功能及NMDAR表达的影响

Effects of swimming training on cognitive function and NMDAR expression in rats with cerebral hemorrhage

目的探讨游泳对脑出血(ICH)大鼠认知功能的影响,并分析其相关的神经生物学机制。方法将30只Sprague-Dawley大鼠采用随机数字表法分为3组:假手术组(假手术组),脑出血模型组(模型组),脑出血后游泳组(游泳组);每组10只。模型组和游泳组,将I型胶原酶注入大鼠尾状核建立ICH大鼠模型;造模成功后1 d,游泳训练后1 d、3 d、5 d,采用改良的神经功能缺损评分法(mNSS)评测3组大鼠的神经功能;游泳训练结束后,3组大鼠同时进行4天的Morris水迷宫(MWM)实验,记录3组大鼠4天MWM实验情况,评价3组大鼠的认知功能;MWM检测完毕处死大鼠,免疫荧光法检测N-甲基-d-天冬氨酸受体(NMDAR)的表达;Western blot法检测海马CA3区NMDAR 1(NR1)和NMDAR 2B(NR2B)的表达。结果双因素重复测量方差分析显示,与模型组相比,游泳组的mNSS评分降低(P<0.05),且模型组和游泳组随时间的变化评分降低(P<0.05),而组间和时间交互作用差异无统计学意义(P>0.05);与模型组相比,游泳组的逃避潜伏期长(P<0.05),目标象限时间占比少(P<0.05),且模型组和游泳组随时间的变化逃避潜伏期缩短,目标象限时间占比增大(P<0.05),而组间和时间交互作用差异无统计学意义(P>0.05);免疫荧光分析显示,与模型组相比较,游泳训练组海马CA3区NMDAR的表达下降,差异有统计学意义(P<0.05);Western blot分析显示,与模型组相比较,游泳训练组海马CA3区NR1和NR2B的表达下降,差异有统计学意义(P<0.05)。结论游泳可下调海马CA3区NR1和NR2B的表达水平,其可能是改善ICH大鼠的认知功能障碍的分子机制。

Objective To explore the effect of swimming training on cognitive function in rats with intracerebral hemorrhage(ICH)and to analyze its related neurobiological mechanism.Methods A total of 30 Sprague-Dawley rats were randomly divided into three groups:sham-operatedgroup,intracerebral hemorrhage model group and swimming group,undergoing swimming training after ICH.The ICH model was induced by infusion of type I collagenase into the caudatenucleus of rats.The neurological function was evaluated by a modified neurological severity score(mNSS)after 1d of successful model building and 1 d,3 d,5 d of swimming training.Morris water maze(MWM)test was performed at the same time in three groups to evaluate thecognitive function in rats after swimming training.After MWM detection,the rats were sacrificed and immunohistochemical staining was used to evaluate the expression of N-methyl-d-aspartate receptor(NMDAR)in hippocampus of rats.The expressions of N-methyl-d-aspartate receptor 1(NR1)and N-methyl-d-aspartate receptor 2B(NR2B)in CA3 region of the hippocampus were evaluated by Western blot.Results Two-factor repeated measure ANOVA showed thatcompared with the model group,mNSS scores in the swimming group were lower(P<0.05),and the scores of the model group and the swimming group decreased over time(P>0.05),and there were no significant differences in inter-group and temporal interactions(P<0.05).Compared with the model group,the escape latency of the swimming group was longer(P<0.05),with less target quadrant time proportion(P<0.05),and the escape latency of the model group and the swimming group decreased with the change of time,the proportion of target quadrant time increased(P<0.05),and there were no significant differences in inter-group and temporal interactions(P>0.05).Immunohistochemical staining analysis showed that compared with the model group,swimming training significantly decreased the expression of NR1 and NR2B in CA3 region of the contralateral hippocampus(P<0.05).Western blot analysis showed that compared with the model group,swimming training significantly decreased the expressionof NR1 and NR2B in CA3 region of the contralateral hippocampus(P<0.05).Conclusion Swimming training can improve the cognitive function of ICH rats by down-regulating the expression of NR1 and NR2B in hippocampal CA3 region.