白芍总苷对脑缺血大鼠学习记忆能力及海马CA1区神经元的保护作用

Effect of Total Glucosides of Paeony on Learning and Memory Ability and Protective Effect of Neurons in Hippocampal CA1 Region of Cerebral Ischaemia Rats

目的:研究白芍总苷对脑缺血大鼠学习记忆能力的影响以及对海马CA1区神经元的保护作用并初探其机制。方法:通过结扎双侧颈总动脉制备大鼠脑缺血模型,术后第二天开始连续28 d灌胃给药白芍总苷(50、100、200 mg·kg^(-1)),每天1次。28 d后,通过Morris水迷宫实验和跳台实验评价大鼠学习记忆能力;HE染色观察海马CA1区神经元形态,TUNEL染色观察海马CA1区神经元凋亡状况,免疫组织化学(IHC)法检测海马Bcl-2、Bax表达,检测抗氧化酶活性和MDA含量。结果:100、200 mg·kg^(-1)白芍总苷能够显著缩短脑缺血大鼠逃避潜伏期,显著缩短跳台潜伏期、增加跳台次数(P<0.05或P<0.01);明显改善海马CA1区神经元病理性形态结构变化和细胞凋亡状况,显著降低凋亡指数(Apoptosis Index,AI)(P<0.01),显著上调海马Bcl-2表达、下调Bax表达,提高Bcl-2/Bax值(P<0.05或P<0.01),显著改善抗氧化酶(SOD、CAT、GSH-Px)活性并降低MDA含量(P<0.05或P<0.01)。结论:白芍总苷具有改善脑缺血大鼠学习记忆能力的作用;可能与其抑制海马CA1区神经元病变、调节Bcl-2和Bax表达、抑制海马CA1区细胞凋亡有关。

Objective:To study the effect of total glucosides of paeony on learning and memory ability of cerebral ischemia rats and the protective effect on neurons in hippocampal CA1 region and explore its mechanism.Methods:The cerebral ischemia model was established by ligating bilateral common carotid artery,the total glucosides of paeony(50,100,200 mg·kg-1)were administered by intragastric administration for 28 days on the second day after operation,once a day.After 28 d,Morris water maze test and platform test were used to evaluate the learning and memory ability of rats.The morphological changes of neurons in hippocampus CA1 region were observed by HE staining,the cell apoptosis were observed after TUNEL staining,the expression of Bcl-2 and Bax were examined by IHC,the activity of antioxidant enzymes and malondialdehyde(MDA)in hippocampus tissue were measured.Results:The total glucosides of paeony(100,200 mg·kg-1)could significantly shorten the time of escape latency in cerebral ischemia rats,significantly shorten the time of platform latency and increase the number of jumpers(P<0.05 or P<0.01),significantly improve hippocampal CA1 neuronal pathological changes and apoptosis,significantly decrease the apoptosis index(AI)(P<0.01),significantly up-regulate the expression of Bcl-2 and down-regulated the expression of Bax,increase the Bcl-2/Bax ratio(P<0.05 or P<0.01),significantly improve antioxidant enzymes(SOD,CAT,GSH-Px)activity and decrease MDA content(P<0.05 or P<0.01).Conclusion:The total glucosides of paeony have improvement effects on the ability of learning and memory in cerebral ischemia rats,which perhaps related to inhibit the neuronal lesions in hippocampal CA1 neurons,alter the expression of Bcl-2 and Bax,suppress hippocampal CA1 neurons apoptosis.