摘要
目的研究β淀粉样蛋白(Aβ)在大鼠癫癎(EP)和阿尔茨海默病(AD)共病模型中作用的神经网络和病理改变的相关性。方法 6~8周成年雄性Wistar大鼠40只,随机分为Aβ1-42组、Aβ1-42+毛果芸香碱(Pilo)组、磷酸盐缓冲液(PBS)组和PBS+Pilo组(均n=10)。采用脑立体定位仪将Aβ1-42注入Wistar大鼠海马CA3区,2周后进行Morris水迷宫实验检测大鼠AD模型是否成功。AD模型制备成功后腹腔注射氯化锂-Pilo制备大鼠慢性癫癎模型。采用改良Timm染色法观察各组大鼠海马齿状回苔藓纤维芽生(MFS)水平。结果注射Aβ1-42制备大鼠AD模型后,Morris水迷宫实验表明AD大鼠模型制备成功。制备大鼠癫癎模型后:改良Timm染色显示,Aβ1-42+Pilo组与PBS+Pilo组比较,海马齿状回MFS染色强度显著增强(P <0. 05);Aβ1-42组海马齿状回也观察到MFS染色强度增强,但与PBS+Pilo组比较差异无显著性(P> 0. 05);PBS+Pilo组MFS染色强度与PBS组比较显著增强(P <0. 01);Aβ1-42组MFS染色强度与PBS组比较显著增强(P <0. 01)。结论 MFS代表脑内异常网络连接,Aβ致大鼠认知功能下降与海马齿状回MFS染色增强有关;癫癎合并AD的共病病理基础可能与Aβ致AD大鼠脑内MFS水平显著增加有关;Aβ与癫癎合并AD的神经网络、病理改变间具有相关性。
Aim To study the correlation of the neural network and pathology in comorbidity between epilepsy( EP) and Alzheimer’s disease( AD) by β-amyloid protein( Aβ) in Wistar rats. Methods 40 male Wistar rats were randomly divided into a Aβ1-42+ pilocarpine( Pilo) group,a Aβ1-42 group,a phosphate buffer solution( PBS) + Pilo group and a PBS group,with 10 rats in each group. Aβ1-42 was injected into the hippocampal CA3 region of the Wistar rats,and the Morris water maze test was observed after 2 weeks. The statistical analysis software was used to detect whether the AD model rat was successful.After the model was successfully made,the rat model of chronic EP was established by intraperitoneal injection of LiCl-Pilo. The mossy fiber sprouting( MFS) level of dentate gyrus( DG) in hippocampus was observed by modified Timm’s staining. Results The results of Morris water maze test showed that the AD model rat was successfully prepared. After the rat EP model prepared,the MFS staining of hippocampal DG was obviously stronger in Aβ1-42+ Pilo group than that in PBS + Pilo( P < 0. 05) group,In Aβ1-42 group,the MFS staining of hippocampal DG was also obviously increased and there was no significant difference compared with PBS + Pilo group( P > 0. 05). There was significant difference in the intensity of MFS staining between PBS + Pilo group and PBS group( P < 0. 01). The intensity of MFS staining was also significantly increased in Aβ1-42 group than that in PBS group( P < 0. 01). Conclusion ① The incline of cognitive of rats induced by Aβ have some relationship with MFS staining of hippocampal DG,MFS staining represents the abnormal network existed in brain of rats. ②The structure basis of comorbidity between EP and AD may have relationship to the increased level of MFS staining of hippocampal DG of the Wistar rats by Aβ,and there have some correlation of the neural network and pathology change in comorbidity between EP and AD by Aβ in the Wistar rats.
作者
郑乃智
王敏
赵娟
张彦妹
ZHENG Nai-zhi;WANG Min;ZHAO Juan;ZHANG Yan-mei(Department of Neurology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao 266011 , China;Department of Neurology, Cao County People Hospital, Heze City , Heze 274400, China)
出处
《中国临床神经科学》
2019年第3期252-258,共7页
Chinese Journal of Clinical Neurosciences
关键词
Β淀粉样蛋白
癫癎
阿尔茨海默病
共病
网络
β-amyloid protein
epilepsy
Alzheimer's disease
comorbidity
network
