高压氧及Notch信号阻断剂对大鼠颅脑损伤后海马区神经干细胞增殖分化的影响

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摘要目的观察高压氧及Notch信号阻断剂（DAPT）对大鼠颅脑损伤后内源性神经干细胞增殖分化的影响。方法100只成年健康Wistar大鼠随机平均分为假手术组、颅脑损伤组、DAPT{N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-Sphenylglycinet-butylester}组、高压氧组及二甲基亚砜（DMSO）组，应用改良的自由落体方法制备脑损伤模型，用免疫荧光双标记染色法观察伤后7、14、21 d及28 d大鼠海马区神经干细胞增殖分化。结果颅脑损伤组、DAPT和高压氧组海马区 BrdU/nestin 双标阳性细胞数，在伤后 7 d 为（14.2±1.3）、（11.4±1.7）个和（22.3±1.5）个，在伤后14 d 为（9.6±0.7）、（6.9±2.1）个和（13.8±1.4）个，在伤后 7 d 较伤后 14 d 明显增多（P＜0.05）；与颅脑损伤组比较，DAPT组在伤后7 d及14 d双标阳性的细胞数明显减少（P＜0.05）；高压氧组在伤后7 d及14 d双标阳性的细胞数明显增多（P＜0.05）。结论高压氧能促进内源性神经干细胞增殖分化，Notch信号阻断剂抑制了内源性神经干细胞增殖分化。

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	杨永凯
	张帆
	韦浩
	周晓辉
	陈春美
	王春华
	涂献坤

关键词 ：高压氧, 颅脑损伤, 神经干细胞, Notch通路, 增殖分化

Abstract：Objective To observe the effects of hyperbaric oxygen therapy and DAPT on the proliferation and differentiation of endogenous neural stem cells after traumatic brain injury.Methods 100 adult Wistar rats were randomly divided into sham-operation group,traumatic brain injury group,DAPT group,hyperbaric oxygen therapy group and DMSO group.Animal models of craniocerebral trauma were made using the improved free-fall method in the rats.The proliferation and differentiation of neural stem cells of the DG brain tissue was detected by BrdU labeling fluorescence immunocytochemistry at the 7,14,21 d and 28 d after injury.Results The BrdU and nestin positive cells of the traumatic brain injury group,DAPT group and hyperbaric oxygen therapy group began to increase from the 7 d(14.2±1.3,11.4±1.7,22.3±1.5)to the 14 d after injury(9.6±0.7,6.9±2.1,13.8±1.4).Compared with the 14 d,the BrdU and nestin positive cells significantly increased 7 d after injury(P＜0.05).Compared with the traumatic brain injury group,the BrdU and nestin positive cells significantly decreased in the DAPT group 7 d and 14 d after injury(P＜0.05).Compared with the traumatic brain injury group,the BrdU and nestin positive cells significantly increased in the hyperbaric oxygen therapy group 7 d and 14 d after injury (P＜0.05).Conclusion Hyperbaric oxygen therapy can enhance the proliferation and differentiation of endogenous neural stem cells after traumatic brain injury.Notch signal channel blocker can restrain the proliferation and differentiation of endogenous neural stem cells after traumatic brain injury.

Key words： Hyperbaric oxygen Traumatic brain injury Neural stem cells Notch signal channel Proliferation and differentiation

基金资助:福建省自然科学基金资助项目（2015J01498）；福建省福州市卫生计生科研创新团队培育项目（2013-S-wt1）；福建医科大学非直属附属医院科研发展专项课题（FZS 13002Z）

引用本文:

杨永凯;张帆;韦浩;周晓辉;陈春美;王春华;涂献坤. 高压氧及Notch信号阻断剂对大鼠颅脑损伤后海马区神经干细胞增殖分化的影响[J]. 中国当代医药, 2017, 24(28): 7-10.
YANG Yong-kai;ZHANG Fan;WEI Hao;ZHOU Xiao-hui;CHEN Chun-mei;WANG Chun-hua;TU Xian-kun. The effect of hyperbaric oxygen therapy and Notch signal channel blocker on proliferation and differentiation of neural stem cells in rats with traumatic brain injury. 中国当代医药, 2017, 24(28): 7-10.

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