CAJ | 학술논문

目的研究Aβ1-42寡聚体诱导的阿尔茨海默病(AD)模型大鼠认知功能损害, NALP1、细胞凋亡蛋白酶-1(Caspase-1)在AD模型大鼠大脑皮质和海马的表达。方法将Morris水迷宫初筛后的60只大鼠随机均分为：D-半乳糖组、Aβ1-42纤维组、Aβ1-42寡聚体组、假手术组。分别以Aβ1-42纤维和Aβ1-42寡聚体双侧海马注射建立 AD大鼠模型,D-半乳糖组腹腔注射D-半乳糖,假手术组海马注射等量生理盐水。经Morris水迷宫检测其行为学变化,采用免疫组化法、RT-PCR法观察NALP1、Caspase-1在大鼠海马的表达。结果与假手术组相比,其余3组大鼠学习记忆能力明显下降(P<0.05),以Aβ1-42寡聚体组最明显；免疫组化法显示Aβ1-42寡聚体组海马Caspase-1免疫反应阳性神经元数目显著增加,RT-PCR法显示与Aβ1-42纤维组、D-半乳糖组和假手术组比较,Aβ1-42寡聚体组海马Caspase-1和NALP1 mR-NA表达增强,差异有统计学意义(P<0.05)。结论Aβ1-42寡聚体海马注射可导致大鼠认知功能障碍,上调NALP1及Caspase1表达。 NALP1及Caspase1可能在Aβ1-42寡聚体介导的大鼠认知功能障碍起重要作用,其作用机制有待进一步研究。
목적연구Aβ1-42과취체유도적아이자해묵병(AD)모형대서인지공능손해, NALP1、세포조망단백매-1(Caspase-1)재AD모형대서대뇌피질화해마적표체。방법장Morris수미궁초사후적60지대서수궤균분위：D-반유당조、Aβ1-42섬유조、Aβ1-42과취체조、가수술조。분별이Aβ1-42섬유화Aβ1-42과취체쌍측해마주사건립 AD대서모형,D-반유당조복강주사D-반유당,가수술조해마주사등량생리염수。경Morris수미궁검측기행위학변화,채용면역조화법、RT-PCR법관찰NALP1、Caspase-1재대서해마적표체。결과여가수술조상비,기여3조대서학습기억능력명현하강(P<0.05),이Aβ1-42과취체조최명현；면역조화법현시Aβ1-42과취체조해마Caspase-1면역반응양성신경원수목현저증가,RT-PCR법현시여Aβ1-42섬유조、D-반유당조화가수술조비교,Aβ1-42과취체조해마Caspase-1화NALP1 mR-NA표체증강,차이유통계학의의(P<0.05)。결론Aβ1-42과취체해마주사가도치대서인지공능장애,상조NALP1급Caspase1표체。 NALP1급Caspase1가능재Aβ1-42과취체개도적대서인지공능장애기중요작용,기작용궤제유대진일보연구。
Objective To explore the change of cognition and NALP 1 (NACHT-LRR-PYD containing protein 1)/Caspase-1 expression of hippocampus in AD model, we develop Alzheimer’s disease (AD) rat model induced by Aβ1-42 oligomers. Methods 60 rats screened by Morris water maze were randomly divided into four groups:D-ga-lactose group, Aβ1-42 fiber group, Aβ1-42 oligomers group, Sham-operated group. AD rat models were established by injection bilaterally with Aβ1-42 oligomers or Aβ1-42 fibers into bilateral hippocampus respectively with the ster-eotaxic apparatus, intraperitoneal injection of D-gal was performed in D-galactose group, in sham-operated group bilateral hippocampus were injected with saline solution. Their behavior changes were detected by Morris water maze, immunohistochemisty, RT-PCR analysis were performed to investigate NALP1/Caspase-1 expression of hip-pocampus in rat models. Results Compared with Sham-operated group, learning and memory abilities were de-creased significantly(P<0.05) in the other group, especially in Aβ1-42 oligomers model. Immunohistochemistry assay showed that the number and density of Caspase-1 immune-positive neurnons were increased in hippocampus of Aβ1-42 oligomers rat model. RT-PCR analysis showed that the level of Caspase-1 and NALP1 mRNA expression was significantly enhanced in the hippocampus of Aβ1-42 oligomers model and the differences were statistically signifi-cant (P<0.05). Conclusion Aβ1-42 oligomers injected into hippocampus lead to cognitive dysfunction in AD rat model, which can upregulate NALP1 and Caspase-1 expression. NALP1 and Caspase-1 may play an important role in the Aβ1-42 oligomers-mediated cognitive dysfunction, and its mechanism wait to be further investigated.