摘要
目的:探讨在阿尔茨海默病(AD)脑损伤中β淀粉样蛋白(Aβ)神经毒性对大鼠行为学、内质网应激特异性凋亡因子Caspase12的影响及何首乌提取物二苯乙烯苷(TSG)的干预作用。方法:将大鼠随机分为对照组、假手术组、模型组、TSG组,除对照组外,其余各组采用立体定向仪于海马部位注射微量Aβ1-42诱发大鼠行为学障碍,造AD动物模型,Y电迷宫及Morris水迷宫检测行为学变化,反转录聚合酶链反应(RT-PCR)及免疫印迹法检测制模前(0 d)及制模后第3、21 d(3 d,21 d)的海马神经元特异性凋亡因子Caspase12mRNA及蛋白的表达变化。结果:模型组大鼠Y电迷宫躲避所需的电刺激次数增加,Morris水迷宫测试中潜伏期延长,游泳路程增加及穿越平台次数减少;模型组大鼠CA1区可见大量的凋亡细胞,进一步的分析表明凋亡因子Caspase12在3 d时表达明显增高,21 d时仍有表达,与对照组比较差异有统计学意义(P<0.05)。TSG干预后,大鼠躲避所需的电刺激次数减少,潜伏期缩短,游泳路程缩短,穿越平台次数增加;TSG组凋亡细胞较模型组明显减少;凋亡因子Caspase12在3 d的表达强度较模型组减弱,差异有统计学意义(t=2.717 5,P=0.021 7)。结论:海马神经元在受到Aβ刺激后,可上调内质网特异性的Caspase12凋亡因子表达,启动内质网特异性凋亡途径;TSG可通过下调Caspase12的表达来抵抗Aβ的神经毒性凋亡作用,改善大鼠行为学表现,发挥脑保护作用。
Objective： To observe the effect of tetrahydroxy stilbene glucoside（TSG） on the behavior of rat model and the expression of caspase12 related with endoplasmic reticulum stress induced by Aβ1-42.Methods： Eighty rats were equally randomized into 4 groups（n=20）：the control group,the shamoperated group,the model group and the TSG group.Except for the control group,animal models of AD was induced by Aβ1-42 using stereotactic microinjection to hippocampus.The behavior of rats was measured by using Y-maze and Morris water maze.The expression of caspase 12 in rats hippocampus was detected by Western blotting and RT-PCR at the different time points（0,3 and 21 d）.Results： The number of electric-stimulus in hippocampus significantly increased and the Morris water maze test showed that the escape latency prolonged,swimming distance increased and the times of crossing the exact former platform location decreased both in the model and TSG groups after 21 days compared with those in control group.A large number of apoptotic cells can be found in CA1 area of model rats.Further analysis showed that the expression of caspase12 upgrade and was highest at 3 d and in model group.compared to model group,apoptotic cells was significantly reduced in TSG group.The expression of caspase 12 was decreased at 3 d in TSG group.Conclusion： Initiation of caspase12 apoptosis pathway is possible one of the mechanisms that priming endoplasmic reticulum apoptosis pathway in Aβ neurotoxic injury.TSG from Poly-gonum multiflorum have protective effection on it.
出处
《东南大学学报（医学版）》
CAS
2011年第6期855-860,共6页
Journal of Southeast University(Medical Science Edition)
基金
甘肃省青年科技基金计划项目(1107RJYA059)
关键词
Β-淀粉样蛋白
内质网应激
凋亡
二苯乙烯苷
β-amyloid peptide
endoplasmic reticulum stress
apoptosis
tetrahydroxy stilbene glucoside
