摘要
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 mRNA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。
Objective To explore the change of cognition and NALP 1 （ NACHT-LRR-PYD containing protein 1 ）/ Caspase-I 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-galactose group, Aβ1-42fiber 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 stereotaxic 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 hippocampus in rat models. Results Compared with Sham-operated group, learning and memory abilities were decreased 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 significant （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.
出处
《安徽医科大学学报》
CAS
北大核心
2013年第12期1453-1457,共5页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81260174)
广西自然科学基金资助项目(编号:0499017)
作者简介
孙婧霞，女，硕士研究生；
蒋常文，男，教授，硕士生导师，责任作者，E-mail：jiangchangwen_gl@163．com
