CAJ | 학술논문

目的探讨Aβ1-42寡聚体侧脑室灌注对大鼠大脑皮质Bcl-2、Caspase-3表达的影响。方法采用Morris水迷宫法筛选出逃避潜伏期少于60 s的60只雄性大鼠随机均分为4组：正常组、PBS 对照组、Aβ1-42纤维组、Aβ1-42寡聚体组。右侧脑室注射Aβ1-42纤维体或Aβ1-42寡聚体复制阿尔茨海默病( AD)模型；PBS对照组注射等量的PBS；正常组不作任何处理。模型建立后第4周,采用Morris水迷宫测试大鼠学习记忆能力的变化,用RT-PCR法检测大鼠皮质Bcl-2、Caspase-3 mRNA的表达,用Western blot法检测AD大鼠皮质Bcl-2蛋白表达以及Caspase-3活性。结果造模后,与正常组和PBS对照组相比, Aβ1-42纤维组、Aβ1-42寡聚体组逃避潜伏期较造模前均延长(P<0.05),Aβ1-42寡聚体组大鼠逃避潜伏期长于 Aβ1-42纤维组大鼠的逃避潜伏期；Aβ1-42纤维组及Aβ1-42寡聚体组脑组织中Bcl-2表达均下调(P<0.05),Caspase-3表达均上调(P<0.05),以Aβ1-42寡聚体组较为显著。结论 Aβ1-42纤维、Aβ1-42寡聚体均可导致大鼠认知功能障碍,抑制大鼠皮质Bcl-2 mRNA表达,上调Caspase-3 mRNA表达,活化Caspase-3,其中,Aβ1-42寡聚体对Bcl-2 mRNA和Caspase-3 mRNA表达影响较大。
목적탐토Aβ1-42과취체측뇌실관주대대서대뇌피질Bcl-2、Caspase-3표체적영향。방법채용Morris수미궁법사선출도피잠복기소우60 s적60지웅성대서수궤균분위4조：정상조、PBS 대조조、Aβ1-42섬유조、Aβ1-42과취체조。우측뇌실주사Aβ1-42섬유체혹Aβ1-42과취체복제아이자해묵병( AD)모형；PBS대조조주사등량적PBS；정상조불작임하처리。모형건립후제4주,채용Morris수미궁측시대서학습기억능력적변화,용RT-PCR법검측대서피질Bcl-2、Caspase-3 mRNA적표체,용Western blot법검측AD대서피질Bcl-2단백표체이급Caspase-3활성。결과조모후,여정상조화PBS대조조상비, Aβ1-42섬유조、Aβ1-42과취체조도피잠복기교조모전균연장(P<0.05),Aβ1-42과취체조대서도피잠복기장우 Aβ1-42섬유조대서적도피잠복기；Aβ1-42섬유조급Aβ1-42과취체조뇌조직중Bcl-2표체균하조(P<0.05),Caspase-3표체균상조(P<0.05),이Aβ1-42과취체조교위현저。결론 Aβ1-42섬유、Aβ1-42과취체균가도치대서인지공능장애,억제대서피질Bcl-2 mRNA표체,상조Caspase-3 mRNA표체,활화Caspase-3,기중,Aβ1-42과취체대Bcl-2 mRNA화Caspase-3 mRNA표체영향교대。
Objective To investigate the changes in cortical Bcl-2 and Caspase-3 expression after microinfusion Aβ1-42 oligomers into right lateral cerebral ventricle. Methods After screening with Morris water maze, 60 rats with escape latency less than 60 s were randomly assigned equally into four groups: the naive group, PBS control group and Aβ1-42 fiber group and Aβ1-42 oligomers group. The rats in Aβoligomers and fiber group were infused Aβ1-42 oligomers or Aβ1-42 fiber into right cerebral ventricle to establish Alzheimer’s disease( AD) rat model;PBS control group received the same volume of PBS; naive group received no treatment. Four weeks after modeling, Morris water maze were performed to detect the changes in the ability of learning and memory in rats. RT-PCR as-say was used to detect the expression of cortical Bcl-2 mRNA and Caspase-3 mRNA in AD rats. Western blot assay was carried out to investigate cortical Bcl-2 protein expression and activity of Caspase-3 protein. Results Com-pared with naive and PBS control group, the escape latency in Aβ1-42 fiber group and Aβ1-42 oligomers group were prolonged than before modeling (P<0.05),the escape latency in Aβ1-42 oligomers group was longer than in Aβ1-42 fiber group;the cortical Bcl-2 mRNA expression in Aβ1-42 fiber and oligomers group were decreased( P<0.05 ) , and the Caspase-3 mRNA expression and activity were increased ( P<0.05 ) . The above-mentioned chan-ges of Bcl-2 and Caspase-3 mRNA expression in Aβ1-42 oligomers group were more prominent than that in Aβ1-42 fiber group. Conclusion Aβ1-42 fiber, Aβ1-42 oligomers can all lead to cognitive dysfunction, up-regulating Caspase-3 mRNA expression, increasing the activity of Caspase-3 protein and inhibiting Bcl-2 expression in AD rats, but the effects of Aβ1-42 oligomers on Caspase-3 and Bcl-2 mRNA expression are greater than in Aβ1-42 fi-ber.