缺氧缺血性脑损伤发病中神经干细胞变化规律初探

Changes of neural stem cells following hypoxic-ischemic brain damage

摘要:

目的：探讨缺氧缺血性脑损伤后神经干细胞(NSCs)的变化规律。方法：取新生7日SD大鼠随机分为正常对照组、缺氧组和缺氧缺血组。每组再根据处死时间点随机分成3 h,6 h,1 d,3 d,7 d,14 d,21 d 7个亚组(n=10)。缺氧缺血组大鼠分离并结扎左颈总动脉,置于密闭缺氧箱2.5 h,缺氧组不结扎血管,仅缺氧2.5 h。免疫组织化学检测海马、皮层及纹状体区阳性NSCs数。结果：正常7日龄大鼠脑组织存在NSCs,且呈明显的区域性分布,在10日龄后数目逐渐减少。缺氧组及缺氧缺血组大鼠NSCs较正常组增多,差异有显著性,在缺氧后3d(10日龄)时达高峰,后逐渐减少,缺氧组在缺氧后21 d(28日龄)时仍高于正常组。结论：H IBD发病中早期NSCs增殖;NSCs随着病情的演变开始减少;早期采用NSCs干预治疗可能为临床治疗H IBD提供重要途径。

Abstract:

OBJECTIVE: This study examined the changes of neural stem cells (NSCs) following hypoxic-ischemic brain damage (HIBD) in order to provide a basis for clinical use of NSCs. METHODS: Neonatal 7-day-old rats were randomly assigned into three groups: Normal control, Hypoxic and Hypoxic-ischemic groups. The Hypoxic-ischemic group was subjected to the left common carotid artery ligation followed by 8% oxygen exposure for 2.5 hrs.The Hypoxic group was exposed to 8% oxygen for 2.5 hrs but without the carotid artery ligation.The subjects were sacrificed at 3 and 6 hrs, and 1, 3, 7, 14 and 21days after hypoxia/ischemia (10 rats at each time point). The number of NSCs from brain tissues of rats was detected with hematoxylin-eosin staining and immunohistochemistry. RESULTS: NSCs were presented in the normal brain tissues of neonatal rats and were reduced at 10 days postnatal.The NSCs in the Hypoxic and the Hypoxic-ischemic groups increased after hypoxia/ischemia and were significantly higher than that in the Normal control group at 6 hrs after hypoxia and at 1 day after hypoxia-ischemia. The NSCs number peaked at 3 days after hypoxia/ischemia and then decreased gradually but remained higher than that in the Normal control group at 21 days after hypoxia. CONCLUSIONS: NSCs may proliferate in the early phase of HIBD but decrease while the damage is developing. Early NSCs intervention for the treatment of HIBD appears to be promising.