血管性痴呆大鼠脑室管膜下区和齿状回神经干细胞增殖分化的动态变化

The long-term dynamic changes of proliferation and differentiation of neural stem cells in subventricular zone and dentate gyrus of vascular dementia rats

目的:观察血管性痴呆(VD)模型大鼠脑室管膜下区(SVZ)和齿状回(DG)神经干细胞(NSCs)增殖与功能分化的动态变化。方法:采用双侧颈总动脉夹闭再灌注同时腹腔注射硝普纳建立血管性痴呆模型,在15 d,1月,2月,4月等时间点,采用Morris水迷宫检测和BrdU和/或神经颗粒素(Ng)标记的免疫荧光单标和双标技术分别观察大鼠的学习记忆能力变化和NSCs的增殖与功能分化情况。结果:与假手术组相比,模型组大鼠逃逸潜伏期在各时间点均明显延长(P<0.01)。模型组大鼠SVZ和SGZ区BrdU阳性细胞在15 d和1月时间点均较假手术组相应时间点明显增加(P<0.01),SVZ区在2月和4月时间点BrdU阳性细胞仍多于假手术组(P<0.01),尤其以15 d时间点数量最多。模型组DG区BrdU/Ng双标阳性细胞在1月时间点明显多于假手术组(P<0.05)。结论:VD大鼠SVZ和SGZ区的NSCs增殖在一定时间内明显增强,并可分化为表达Ng的新生神经元,对VD脑损伤后的神经再生与功能修复可能起到部分代偿作用。

Objective： To observe the dynamic changes of proliferation and differentiation of neural stem cells （NSCs） in subventricular zone （SVZ） and dentate gyrus （DG） in vascular dementia （VD） rats. Methods： VII） models were established by repeatedly clipping the common carotid arteries of the rat in combination with an intraperitoneal injection of sodium nitroprusside solution in anesthetized SD rats. Morris maze test was used to detect the learning and memory ability of the rats and immunefluorescence single and double labeling method to detect the proliferation and differentiation of neural stem cells and the expression of neurogranin （Ng） at 15 d, 1 month, 2 month, 4 month time points. Results： Compared with sham-operated gup, the escape latency of model group rats were significantly longer at all the time points （ P 〈 0.01）. The BrdU positive cells in SVZ and DG of VD model groups were markedly increased in comparison with sham-operated group at 15 d and 1 month time point （ P 〈 0.01）, and the number of BrdU positive cells in SVZ of model groups were still larger than that of sham-operated group at 2 month and 4 month time point （ P 〈 0.01）. In model group, the number of the BrdU/Ng double staining ceils were increased and higher than that in sham-operated groups （ P 〈0.05）. Conclusion： The proliferation of NSCs can be enhanced noticeably in a certain time in SVZ and DG region and NSCs differentiate into mature neurons with the expression of Ng in DG region in VD rats, which may play some compensatory roles in the nerve regeneration and functional repairment after cerebral injury of VD.