丁苯酞减轻阿尔兹海默病大鼠海马神经元凋亡

›› 2019, Vol. 39 ›› Issue (12): 1746-1751.

丁苯酞减轻阿尔兹海默病大鼠海马神经元凋亡

刘雅林¹,谢兰兰²,王丽云²,赵瑞杰²,许峰²,王文胜²

1. 河北省邢台市人民医院
2. 邢台市人民医院

收稿日期:2019-03-14 修回日期:2019-09-23 出版日期:2019-12-05 发布日期:2019-12-04
通讯作者: 刘雅林 E-mail:3525193849@qq.com
基金资助:
邢台市科技计划项目

Butylphthalide attenuates apoptosis of hippocampal neurons in Alzheimer's disease rats

Received:2019-03-14 Revised:2019-09-23 Online:2019-12-05 Published:2019-12-04

摘要/Abstract

摘要： 目的探讨丁苯酞对阿尔兹海默病（AD）大鼠海马神经元凋亡的影响。方法将大鼠分为对照组、AD模型组（腹腔注射D-半乳糖和三氯化铝）、丁苯酞低、中和高剂量组（25、50和100 mg/kg）为灌胃干预组，每组12只。流式细胞仪检测海马神经元凋亡，HE观察海马CA1区神经元形态变化；real-time-PCR检测海马神经元中Tau蛋白及凋亡因子Bcl-2、bax和caspase3 mRNA表达；Western blot检测海马神经元中mTOR、AKT和GSK-3β蛋白表达。结果与对照组比较，模型组大鼠第1～5 d逃避潜伏期及第1次找到原始平台时间明显延长，跨越原始平台次数明显减少，海马神经元凋亡率均明显升高，模型组Tau、Bax、caspase3 mRNA表达升高；Bcl-2 mRNA表达及mTOR、AKT、GSK-3β蛋白表达量均降低（P＜0.05）；与模型组比较，丁苯酞低、中和高剂量组第3～5 d逃避潜伏期及第1次找到原始平台时间明显缩短，跨越原始平台次数明显增加，海马神经元凋亡率均明显降低，Tau、Bax、caspase3 mRNA降低，Bcl-2 mRNA及mTOR、AKT、GSK-3β蛋白表达量均升高（P＜0.05）。结论丁苯酞具有显著的抑制AD大鼠海马神经元凋亡作用，其作用机制可能与抑制Tau蛋白、调节凋亡因子和激活mTOR/AKT/GSK-3β信号通路有关，但具体机制还有待进一步分析。

关键词: 阿尔兹海默病, 丁苯酞, 海马神经元, mTOR/AKT/GSK-3β信号通路

Abstract: Objective To investigate the effect of butylphthalide on apoptosis of hippocampal neurons in rats with Alzheimer's disease (AD). Methods The rats were divided into control group, AD model group and the rats were intraperitoneally injected with D-galactose and aluminium trichloride, the low, medium and high dose groups of butylphthalide (25, 50 and 100 mg/kg) were given intragastric administration, 12 rats in each group. Flow cytometry was used to detect the apoptosis of hippocampal neurons, HE was used to observe the morphological changes of hippocampal CA1 neurons, real-time-PCR was used to detect the expression of Tau protein and apoptotic factors Bcl-2, Bax and caspase-3 mRNA in hippocampal neurons, and Western blot was used to detect the expression of mTOR, AKT and GSK-3β in hippocampal neurons. Results Compared with the control group, the escape latency and the first time to find the original platform of model group were significantly prolonged, the number of times to cross the original platform was significantly reduced, and the apoptotic rate of hippocampal neurons was significantly increased, and the expression of Tau, Bax and caspase-3 mRNA increased, while the expression of Bcl-2 mRNA and mTOR, AKT and GSK-3β decreased in the model group (P < 0.05). Compared with the model group, the escape latency and the first time to find the original platform in the low, medium and high dose butylphthalide groups were significantly shortened in the 3rd to 5th day, the number of times to cross the original platform was significantly increased, and the apoptotic rate of hippocampal neurons was significantly reduced, and the expression of Tau, Bax and caspase-3 mRNA decreased, while the expression of Bcl-2 mRNA and mTOR, AKT and GSK-3β increased (P<0.05). Conclusions Butylphthalide can significantly inhibit the apoptosis of hippocampal neurons in AD rats, its mechanism may be related to inhibition of Tau protein, regulation of apoptosis factors and activation of mTOR/AKT/GSK-3β signaling pathway.

Key words: Alzheimer's disease, Butylphthalide, Hippocampal neurons, MTOR/AKT/GSK-3β signaling pathway

刘雅林谢兰兰王丽云赵瑞杰许峰王文胜. 丁苯酞减轻阿尔兹海默病大鼠海马神经元凋亡[J]. , 2019, 39(12): 1746-1751.