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目的：探讨低氧预处理对神经干细胞(neural stem cells, NSCs)移植治疗脑性瘫痪大鼠的影响及其潜在的神经修复机制。方法：采用1%O2培养6 h对体外人源NSCs进行低氧预处理，检测低氧与常氧条件下血管内皮生长因子(vascular endothelial growth factor, VEGF)及脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的表达差异。建立脑性瘫痪大鼠模型后，将低氧及常氧NSCs分别移植至病灶周围，移植后1周和8周评估移植细胞的存活与分化情况，检测患侧脑组织中VEGF、BDNF的表达水平及RECA-1+血管密度，并通过步态分析系统评价大鼠的运动功能。结果：低氧预处理显著上调NSCs中VEGF和BDNF的表达(P<0.01)。移植后，低氧NSCs移植组NSCs存活率及神经元分化比例高于常氧NSCs移植组，移植低氧NSCs的大鼠脑组织中VEGF和BDNF水平及RECA-1+血管密度显著增加(P<0.05)，步态协调性和肢体运动功能改善(P<0.05)。结论：低氧预处理可通过增强NSCs的神经营养作用，促进细胞在脑内的存活、分化及血管再生，从而改善脑性瘫痪大鼠的神经功能缺陷。
Abstract：Objective: To investigate the effects of hypoxic preconditioning on the therapeutic efficacy of neural stem cells(NSCs)transplantation in cerebral palsy rats and to explore the underlying neurorepair mechanisms. Methods: Human-derived NSCs were preconditioned under hypoxic conditions(1%O2 for 6 h). The expression levels of vascular endothelial growth factor(VEGF) and brain-derived neurotrophic factor(BDNF) were compared between hypoxic and normoxic NSCs. After establishing a rat model of cerebral palsy, hypoxic and normoxic NSCs were transplanted into the perilesional area. The survival and differentiation of grafted cells were examined at 1 week and 8 weeks post-transplantation. VEGF, BDNF expression, and RECA-1~+vascular density in the ipsilateral brain tissue were evaluated, and motor function was assessed using a gait analysis system.Results: Hypoxic preconditioning significantly increased VEGF and BDNF expression in NSCs(P<0.01). After transplantation,hypoxia-preconditioned NSCs showed higher survival and neuronal differentiation rates compared with normoxic NSCs. Moreover, rats receiving hypoxic NSCs exhibited elevated VEGF and BDNF levels, enhanced RECA-1~+vascular density(P<0.05),and improved gait coordination and limb motor function(P<0.05). Conclusion: Hypoxic preconditioning enhances the neurotrophic capacity of NSCs, promotes their survival, differentiation, and angiogenic effects in the brain, thereby alleviating neurological deficits in rats with cerebral palsy.
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基本信息:
DOI：10.16424/j.cnki.cn32-1807/r.2026.02.002
中图分类号:R742.3
引用信息:
[1]王晓华,王伯寅,王庆成,等.低氧预处理增强人源神经干细胞在脑性瘫痪大鼠中的神经修复作用[J].南通大学学报(医学版),2026,46(02):111-117.DOI:10.16424/j.cnki.cn32-1807/r.2026.02.002.
基金信息:
国家自然科学基金资助项目(82201508); 2025年江苏省卫生国际(地区)交流支撑计划资助项目
2026-03-15
2026-03-15