CAJ | 학술논문

目的：观测阿尔茨海默病（AD）中Nicastrin（NCT ）和β-淀粉样蛋白（Aβ）在脑内星形胶质细胞中的表达情况，探讨星形胶质细胞在AD中的病变机制。方法应用荧光免疫组织化学法对5× FAD转基因小鼠海马区染色后，激光共聚焦扫描显微镜观察 Nicastrin、Aβ和星形胶质细胞三者位置关系，半定量分析星形胶质细胞、Nicastrin和Aβ的表达变化。结果（1）野生型小鼠的海马区中未见Nicastrin和Aβ聚积，突变型小鼠海马的第一亚区（CA1）、第三亚区（CA3）、齿状回（DG）中可见Nicastrin和Aβ共定位于星形胶质细胞。（2）荧光半定量结果显示，Nicastrin、Aβ和星形胶质细胞在突变型小鼠的CA1、CA3、DG区的荧光强度均大于野生型小鼠的相应脑区（P＜0．05）。（3）体视学计数结果显示，突变型小鼠海马的Aβ、Nicastrin和GFAP的阳性共定位数多于野生型小鼠海马的各相应脑区（P＜0．05）。结论 Nicastrin在AD转基因小鼠脑内的星形胶质细胞中表达增多。导致星形胶质细胞损伤的Aβ可能由表达于其中的β-淀粉样前体蛋白切割而成，而非摄取自神经元。
목적：관측아이자해묵병（AD）중Nicastrin（NCT ）화β-정분양단백（Aβ）재뇌내성형효질세포중적표체정황，탐토성형효질세포재AD중적병변궤제。방법응용형광면역조직화학법대5× FAD전기인소서해마구염색후，격광공취초소묘현미경관찰 Nicastrin、Aβ화성형효질세포삼자위치관계，반정량분석성형효질세포、Nicastrin화Aβ적표체변화。결과（1）야생형소서적해마구중미견Nicastrin화Aβ취적，돌변형소서해마적제일아구（CA1）、제삼아구（CA3）、치상회（DG）중가견Nicastrin화Aβ공정위우성형효질세포。（2）형광반정량결과현시，Nicastrin、Aβ화성형효질세포재돌변형소서적CA1、CA3、DG구적형광강도균대우야생형소서적상응뇌구（P＜0．05）。（3）체시학계수결과현시，돌변형소서해마적Aβ、Nicastrin화GFAP적양성공정위수다우야생형소서해마적각상응뇌구（P＜0．05）。결론 Nicastrin재AD전기인소서뇌내적성형효질세포중표체증다。도치성형효질세포손상적Aβ가능유표체우기중적β-정분양전체단백절할이성，이비섭취자신경원。
Objective To examine the expression of Nicastrin and β-amyloid (Aβ) in brain astro-cytes to explore the role of astrocytes in the pathogenesis of Alzheimer's disease (AD) . Methods Using immunofluorescence staining the distributions of Nicastrin ,Aβand astrocytes in the hippocampus of 5 × FAD transgenic mice were observed under laser confocal scanning microscope and the changes in ex-pression levels were also semi-quantitated . Results (1) Nicastrin and Aβwere co-localized in astrocytes of the CA1、CA3 and DG in mutant mice but not found in the hippocampus in wild-type mice . (2) Fluo-rescence semi-quantitative analysis showed that the fluorescence intensity of Nicastrin ,Aβ and astrocytes in the DG ,CA1 ,CA3 of mutant mice was higher than that in wild-type mice(P<0 .05) . (3) Stereologi-cal counting revealed that the total number of positive colocalization cells with Nicastrin ,Aβ and GFAP immunoreactive in mutant mice was greater than that in wild-type mice(P<0 .05) . Conclusion The re-sults indicated that the expression of Nicastrin was significantly increased in the astrocytes of 5 × FAD transgenic mice and Aβ that induced the fastrocytic injury may derive from β-amyloid precursor protein rather than neuronal uptake .