艾地苯醌改善全脑缺血大鼠认知功能及其对海马神经元蛋白表达的影响

Effects of idebenone on the cognitive function and expression of brain-derived neurotrophic factor and tyrosine Kinase receptor B in hippocampus of total cerebral ischemia rat

目的探讨艾地苯醌对全脑缺血(TCI)大鼠认知功能的影响以及海马神经元的保护的可能机制。方法将100只SD大鼠随机分为艾地苯醌低剂量组、艾地苯醌高剂量组、模型组、假手术组,同时将尼莫地平组作为对照组,每组20只。采用两血管阻断法制备大鼠模型,艾地苯醌高剂量组、低剂量组分别以10 mg/kg、3 mg/kg灌服艾地苯醌,对照组以10 mg/kg灌服尼莫地平,给药30 d后,检测各组大鼠水迷宫法行为学、海马组织海马神经元脑源性神经营养因子(BDNF)和酪氨酸激酶受体B(TrkB)的表达变化。结果与假手术组比较,模型组大鼠空间学习记忆能力与探索能力下降(P<0.05),在原平台停留时间、穿越原平台次数显著减少(P<0.05),逃避潜伏期显著增长(P<0.05),海马神经元BDNF mRNA和TrKB mRNA及蛋白表达均显著下降(P<0.05)。与模型组比较,艾地苯醌高、低剂量组大鼠空间学习记忆能力与探索能力明显改善(P<0.05),在原平台停留时间显著延长(P<0.05),穿越原平台次数显著增多(P<0.05),逃避潜伏期显著缩短(P<0.05),海马神经元BDNF mRNA及TrkB mRNA及蛋白表达升高(均P<0.05)。结论艾地苯醌可提高脑海马神经元BDNF及TrkB表达,具有一定的剂量依赖效应,可保护脑海马神经元,改善TCI大鼠学习与记忆能力。

Objective To investigate the effect of idebenone on cognitive function and the protective mechanism of hippocampal neurons in rats with total cerebral ischemia(TCI).Methods 100 SD rats were randomly divided into five groups:low dose group,high dose group,model group and sham operation group,at the same time,nimodipine group was used as the control group,with 20 rats in each group.The model of rats was established by two vessel blocking methods.The high dose group and low dose group were administrated with 10 mg/kg and 3 mg/kg respectively.The control group was administrated with 10 mg/kg nimodipine.After 30 days of administration,the behavioral changes of water maze method and the expression of brain-derived neurotrophic factor(BDNF)and tyrosine Kinase receptor B(TrkB)in hippocampus were detected.Results Compared with the sham operation group,the spatial learning and memory ability and exploration ability of the model group decreased(P<0.05),the time of staying in the original platform and the times of crossing the original platform decreased significantly(P<0.05),the escape latency increased significantly(P<0.05),the mRNA and protein expression of BDNF and TrkB in hippocampal neurons decreased significantly(P<0.05).Compared with the model group,the spatial learning and memory ability and exploration ability of rats in the high and low dose group were significantly improved(P<0.05),the time of staying in the original platform was significantly prolonged(P<0.05),the times of crossing the original platform was significantly increased(P<0.05),the escape latency was significantly shortened(all P<0.05),and the mRNA expression of BDNF and TrkB and protein expression of TrkB in hippocampal neurons were significantly increased(all P<0.05).Conclusion Idebenone can increase the expression of BDNF and TrkB in hippocampal neurons with a dose-dependent effect,which can protect hippocampal neurons and improve the learning and memory ability of TCI rats.