[脑梗死成年大鼠神经干细胞的增殖与分化：一项实验研究]
[Proliferation and differentiation of neural stem cells after cerebral infarction: an experimental study of adult rats].
作者信息
Zhang Bo, Wang Ren-zhi, Yao Yong, Wang Xin, Li Gui-lin, Dou Wan-chen, Tian Shi-qiang, Zheng Tong, Tian Yu
机构信息
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
出版信息
Zhonghua Yi Xue Za Zhi. 2003 Nov 25;83(22):1975-9.
OBJECTIVE
To investigate the proliferation and differentiation of neural stem cells after cerebral infarction(CI) in adult rats.
METHODS
CI animal model was made by ligating the common carotid artery and external carotid artery and inserting a piece of nylon thread into the internal carotid artery among 100 male Wistar rats. Then the rats were randomly divided into 5 groups: group of I day after brain infarction (n = 20), group of 3 days after brain infarction (n = 20), group of 7 days after brain infarction (n = 20), group of 14 days after brain infarction (n = 20), and group of 28 days after brain infarction (n = 20). Twelve rats undergoing sham operation with a piece of nylon thread inserted only into the common carotid artery were used as controls. The rats were killed at different time points and their brains were taken out. The expression of bromodeoxyuridine (BrdU) and Musashil (both used to mark the dividing neural stem cells), and of glial fibrillary acidic protein (GFAP) and neuronal nuclear antigen (NeuN) (both used to mark the differentiating neural stem cells) were determined by immunohistochemistry and immunofluorescence staining.
RESULTS
In the normal brain tissues, only a small amount of BrdU(+) cells were found in the hippocampus. One day after CI the number of BrdU(+) cells began to increase in the hippocampus at the CI side (P < 0.05), peaked 7 days after CI with a number 6 times that at the normal side, began to decrease 14 days after, and almost reached normal 28 days after. The number of BrdU(+)/Musashil(+) cells began to increase 1 day after CI (P < 0.05), peaked 7 days after, began to decrease 14 days after, and almost reached normal 28 days after. The number of BrdU(+)/GFAP(+) cells at the CI side remained almost unchanged after CI. The number of BrdU(+)/NeuN(+) cells began to increase 14 days after CI (P < 0.05) and peaked 38 days after.
CONCLUSION
Cerebral infarction stimulates the proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.
目的
研究成年大鼠脑梗死（CI）后神经干细胞的增殖与分化情况。
方法
将100只雄性Wistar大鼠通过结扎颈总动脉和颈外动脉并向颈内动脉插入一段尼龙线制成CI动物模型。然后将大鼠随机分为5组：脑梗死1天组（n = 20）、脑梗死3天组（n = 20）、脑梗死7天组（n = 20）、脑梗死14天组（n = 20）和脑梗死28天组（n = 20）。12只仅向颈总动脉插入一段尼龙线进行假手术的大鼠作为对照组。在不同时间点处死大鼠并取出大脑。采用免疫组织化学和免疫荧光染色法检测溴脱氧尿苷（BrdU）和Musashil（均用于标记正在分裂的神经干细胞）以及胶质纤维酸性蛋白（GFAP）和神经元核抗原（NeuN）（均用于标记正在分化的神经干细胞）的表达。
结果
在正常脑组织中，仅在海马区发现少量BrdU(+)细胞。CI后1天，CI侧海马区BrdU(+)细胞数量开始增加（P < 0.05），CI后7天达到峰值，为正常侧的6倍，14天后开始减少，28天后几乎恢复正常。BrdU(+)/Musashil(+)细胞数量在CI后1天开始增加（P < 0.05），7天后达到峰值，14天后开始减少，28天后几乎恢复正常。CI侧BrdU(+)/GFAP(+)细胞数量在CI后几乎保持不变。BrdU(+)/NeuN(+)细胞数量在CI后14天开始增加（P < 0.05），38天后达到峰值。
结论
脑梗死刺激内源性神经干细胞增殖，且大多数增殖的神经干细胞分化为神经元。
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