CAJ | 학술논문

目的通过比较阿尔茨海默病(AD)模型小鼠和野生型小鼠视网膜内病理改变情况,探讨AD患者视觉异常的原因. 方法取3月龄、12月龄AD模型小鼠及同窝野生型正常小鼠各10只,采用免疫组化的方法比较2种小鼠视网膜内β-淀粉样蛋白前体蛋白(APP)和β-淀粉样蛋白(Aβ)的表达变化;应用视网膜铺片结合免疫荧光染色的方法比较2种小鼠视网膜内星形胶质细胞的形态及数量变化(通过检测其标志物胶质纤维酸性蛋白). 结果 APP在不同月龄AD模型小鼠和野生型小鼠视网膜内均有表达,但AD模型小鼠视网膜内的表达明显强于同龄野生型小鼠,差异有统计学意义(t=3.232,P=0.018;t=5.797,P=0.001).Aβ在野生型小鼠视网膜内几乎无沉积,而在AD模型小鼠视网膜内12月龄较3月龄表达明显增强,差异有统计学意义(t=6.486,P=0.001).与3月龄野生型小鼠相比,同龄AD模型小鼠视网膜内的星形胶质细胞数量明显增加[(602.60±36.35)个/mm2 vs (309.52±41.55)个/mm2],差异有统计学意义(t=5.309,P=0.006),且突起增多、变短.结论 Aβ的沉积与AD模型小鼠视网膜的神经退行性变密切相关.
목적 통과비교아이자해묵병(AD)모형소서화야생형소서시망막내병리개변정황,탐토AD환자시각이상적원인. 방법 취3월령、12월령AD모형소서급동와야생형정상소서각10지,채용면역조화적방법비교2충소서시망막내β-정분양단백전체단백(APP)화β-정분양단백(Aβ)적표체변화;응용시망막포편결합면역형광염색적방법비교2충소서시망막내성형효질세포적형태급수량변화(통과검측기표지물효질섬유산성단백). 결과 APP재불동월령AD모형소서화야생형소서시망막내균유표체,단AD모형소서시망막내적표체명현강우동령야생형소서,차이유통계학의의(t=3.232,P=0.018;t=5.797,P=0.001).Aβ재야생형소서시망막내궤호무침적,이재AD모형소서시망막내12월령교3월령표체명현증강,차이유통계학의의(t=6.486,P=0.001).여3월령야생형소서상비,동령AD모형소서시망막내적성형효질세포수량명현증가[(602.60±36.35)개/mm2 vs (309.52±41.55)개/mm2],차이유통계학의의(t=5.309,P=0.006),차돌기증다、변단.결론 Aβ적침적여AD모형소서시망막적신경퇴행성변밀절상관.
Objective To compare the expressions of amyloid precursor protein (APP) and amyloid β-protein (Aβ),and astrocyte patterns in the retina between mouse models of Alzheimer's disease (AD) and wild type mice to explore the reasons of disordered vision.Methods Retina were removed from AD mouse models and wild-type controls of three or twelve months old;immunohistochemical staining was performed to observe the expressions of APP and Aβ in the retina;immunofluorescent staining combined with retinal stretched preparation was performed to observe the morphological and density changes of astrocytes in the retina by detecting the glial fibrillary acidic protein level.Results APP positive cells were observed in the retina of both APP/PS1 double transgenic mice and wild-type littermates,while a significant increase of APP expression was seen in the APP/PSI double transgenic mice as compared with that of wild-type controls (t=3.232,P=0.018; t=5.797,P=0.001).Aβ deposition was hardly observed in the retina of wild-type mice; however,its depositions were significantly increased in the retina of AD models with an age-dependant manner (t=6.486,P=0.001).Meanwhile,a significant increase of numbers of astrocytes with shorter and numerous processes ([602.60 ±36.35]cell/mm2 vs.[309.52±41.55] cell/mm2) were seen in the retina of AD mouse models as compared with that of wild type ones (t=5.309,P=0.006).Conclusion Aβ deposition is increased with age in the retina of AD model mice,which is accompanied with reactive astrogliosis,which indicates that Aβ deposition is closely related to the neurodegeneration of retina in the APP/PS 1 double transgenic AD models.