嗅鞘细胞移植入淀粉样前体蛋白转基因小鼠脑内降低β淀粉样蛋白沉积

目的 观察嗅鞘细胞移植入淀粉样前体蛋白(APP)转基因小鼠脑内后的存活和迁移状况及其对模型β淀粉样蛋白沉积的作用,以进一步探索嗅鞘细胞移植对阿尔茨海默病的治疗效果.方法 取自发绿色荧光蛋白的新生3d龄增强型绿色荧光蛋白(EGFP)转基因小鼠,体外分离培养嗅球嗅鞘细胞,在小鼠脑立体定位仪的固定下,参照AP小鼠脑立体定位图谱,将收集的嗅鞘细胞移植入APP转基因小鼠脑内.移植1个月后,取脑组织冷冻切片,在双光子共焦显微镜下观察细胞存活和迁移状况并采集图像.移植1个月后,行荧光免疫组织化学和免疫印迹法检测淀粉样蛋白沉积,每组4只.结果 嗅鞘细胞移植入APP转基因小鼠脑内存活良好,并以移植点为中心向外迁移,部分绿色荧光细胞呈现成血管现象,移植之后APP转基因小鼠脑内的β淀粉样蛋白沉积减少,APP表达明显减少(P<0.05).结论 嗅鞘细胞对减少APP转基因小鼠脑内淀粉样蛋白沉积有一定帮助.

Olfactory ensheathing cells transplanation reduced amyloid burden in amyloid precursor protein transgenic mouse model

Objective To observe the survival and migration of olfactory ensheathing cells (OECs) after transplanted into amyloid precursor protein (APP) transgenic mice and investigate its therapeutical effect on Alzheimer disease. Methods OECs from olfactory ensheathing bulb of enhanced green fluorescent protein(EGFP) transgenic mice were isolated, then transplanted into an APP transgenic mice. Stereotaxic coordinates and anterior-posterior were appilicated for microinjection. Confocal microscope was used to observe the survival and migration of the cells, immunohistochemistry and Western blotting were carried out to survey amyloid burden, 4 mice in each group. Results The results showed that OECs survived well and migrated away from injection site after transplanted into APP transgenic mice, the vascular phenomena of OECs was also observed, and the therapy reduced amyloid burden of Alzheimers disease model.Quantitative test showed that APP reduced significantly（EM>P/EM><0.05）. Conclusion Olfactory ensheathing cells do some help to reduce the amyloid burden in the brain of APP transgenic mice.