运动对内质网应激诱导阿尔茨海默病模型大鼠海马细胞凋亡的影响

目的:探讨运动对内质网应激诱导阿尔茨海默病大鼠海马神经细胞凋亡的影响及其机制。方法:45只雄性SD大鼠随机分为假手术组(S)、AD模型组(M)、模型训练组(E),每组15只。在立体定位仪下向大鼠两侧海马注射Aβ25-35制造AD模型,TUNEL法检测海马细胞凋亡率的变化,western blot法检测GRP78、Caspase-12、Bcl-2及Bax的表达。结果:与S组比较,M组大鼠海马神经细胞凋亡率增加,内质网应激蛋白GRP78、Caspase-12表达均增加,Bcl-2表达降低,Bax表达升高,差异均有统计学意义(P<0.01);与M组相比,6周游泳训练干预后,E组大鼠细胞凋亡率下降,GRP78、Caspase-12表达均降低,Bcl-2表达升高,Bax表达降低,差异均有统计学意义(P<0.01)。结论:6周的游泳训练可减少AD大鼠海马神经细胞的凋亡,其机制可能是降低内质网应激反应,下调GRP78、Caspase-12和Bax的表达,同时增加Bcl-2的表达,进而促进神经元存活。

Effects of Exercise on Endoplasmic Reticulum Stress Induced the Apoptosis of Hippocampus Cells in the Alzheimer's disease Model Rats

Objective:To explore the effect and mechanism of exercise on endoplasmic reticulum stress induced the apoptosis of hippocampus cells in the Alzheimer’s disease model rats.Methods:45 normal male SD rats were randomly divided into 3 groups with 15 rats in each group,the sham operation(S) group,the AD model(M) group,the exercise model(E) group.The AD model of rats were established by bilateral hippocampus stereotaxic injection of Aβ25-35.The apoptosis rate of hippocampus cells were detected with terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL),and the protein expressions of GRP78,Caspase-12,Bcl-2 and Bax in hippocampus tissues were analyzed using Western blot.Results:The TUNEL-Positive neurons in hippocampus of rats in the group M significantly increased than that in the group S(P<0.01).Western blot showed that the protein expressions of GRP78,Caspase-12,and Bax in the group M increased more significantly than that in the group S(P<0.01) and the expressions of Bcl-2 was conversed.After 6 weeks swimming exercise,compared with the group M,the TUNEL-Positive neurons and the protein expressions of GRP78,Caspase-12,and Bax in the group E significantly decreased(P<0.01) and the expressions of Bcl-2 was significantly increased(P<0.01).Conclusion:The six-week swimming exercise reduced the apoptosis neurons in hippocampus.The mechanism may be that the swimming exercise depress the ER and down-regulated the expressions of GRP78,Caspase-12 and Bax and up-regulated the expressions of Bcl-2 and then promoted the survival of neurons.