神经生长因子和碱性成纤维细胞生长因子对缺氧缺血脑损伤新生大鼠内源性神经干细胞的影响

The therapeutic effect of exogenous nerve growth factor and basic fibroblast growth factor on hypoxic-ischemic encephalopathy in neonatal rats

目的:探讨外源性碱性成纤维细胞生长因子(bFGF)和神经生长因子(NGF)联合用药对大鼠缺氧缺血脑损伤(HIBD)的治疗作用,为探索治疗早产儿脑损伤的有效方法提供科学的实验依据和新的思路。方法:将50只新生7d龄SD大鼠随机分成假手术组(n=10)和HIBD模型组(HI组)(n=40)。HI组又根据A药(NGF)、B药(bFGF)两因素,用药、不用药两个水平,交叉分成4组,分别为生理盐水对照组(n=10)、NGF治疗组(n=10)、bFGF治疗组(n=10)和NGF+bFGF联合治疗组(n=10)。分别观察各组大鼠脑组织大体改变及免疫组化改变,分析两药对于HIBD神经元数目的影响。结果:各组均存在不同程度的脑萎缩,生理盐水对照组最严重,与其他各组相比,差异有显著性。免疫组化结果显示,假手术组和生理盐水对照组海马CA1区的nestin阳性细胞数多于其他各组,其差异有显著性。结论:(1)NGF、bFGF均可提高HIBD后海马区神经元的数量;(2)NGF、bFGF的联合应用可提高对HIBD后海马区神经元的保护作用。

Objective To investigate the neuroprotective effect of exogenous basic fibroblast growth factor （bFGF）and nerve growth factor （NGF） on neurological function in neonatal rat model of hypoxic-ischemic brain damage （HIBD）. Methods Forty HIBD models of neonatal Sprague-Dawley rats were induced by shearing left arteria carotis communis and then being supplied with 8% O2 ＋ 92% N2 for 20 hours. The models were randomly divided into four groups, the bFGF treatment group, the NGF treatment group, the therapeutic alliance group, and the control group, and ten rats were included in each group. The other ten neonatal Sprague-Dawley rats were used as the sham control group. The changes in the brain were observed by optical microscope and the nestin expression in hippoeampal CA1 region were examined by using immunohistochemieal staining and image quantitative analysis 7 days after the surgery. Results Severe or mild encephalanalosis was found in each group, especially in the control group. The numbers of nestin-positive cells in hippocampal CA1 region of the treatment groups were more than those of the sham operation group or the control group （P 〈 0.01）. Conclusions （1） The nestin expression was increased in hippoeampal CA1 region of neonatal rat model of HIBD, it may be attributed to the activation of neural stein cells and the regeneration of neuroeytes after HIBD. （2） Exogenous NGF or bFGF could enhance the nestin expression in the brain of neonatal rat model of HIBD, which may play an important role in restoration of neurons from hypoxia-isehemia brain damage. （3） Applying the two drugs simultaneously may enhance the protective effect on neurons in HIBD.