神经生长因子对缺氧缺血性脑损伤细胞凋亡的影响

背景:细胞凋亡是脑缺氧缺血神经细胞死亡的一种方式,体外试验表明神经生长因子(nervegrowthfactor,NGF)缺乏可诱导神经细胞凋亡。目的:探讨新生儿缺氧缺血性脑损伤(hypoxic-ischemicbraindamageHIBD)与细胞凋亡之间的关系,研究NGF对HIBD的保护作用,为用NGF治疗新生儿HIBD提供理论依据。设计:完全随机设计,对照实验研究。地点与材料:7dSD大鼠40只来源于南京医科大学实验动物中心,体质量约14～18g,雌雄不拘,饲养于屏障环境的SPF级实验动物。干预:40只大鼠制成HIBD动物模型,随机分成两组:HIBD模型对照组20只,NGF治疗组在大鼠缺氧缺血后即刻腹腔注射NGF。主要观察指标:观察NGF对HIBD模型的新生大鼠体质量增长情况、死亡率、左右脑质量影响,并用原位缺口末梢标记(insitunickendlabeling,TUNEL)法检测NGF对缺氧缺血后脑细胞凋亡的影响。结果:HIBD模型NGF治疗组体质量增长明显高于对照组(P<0.01);治疗组实验过程中死亡率明显低于对照组;HIBD模型NGF治疗组与对照组健侧(右侧)脑质量相近,但治疗组患侧(左侧)脑质量犤(0.57±0.02)g犦明显重与对照组犤(0.42±0.1)g,P<0.01犦;治疗组左右脑质量无显著差异,而对照组左右脑质量差异有显著性意义(P<0.01);TUNEL染色所见阳性凋亡细胞,其凋亡特征为胞体缩小、核固缩、核碎

Impact of nerve growth factor on the apoptosis in hypoxic-ischemic brain damage

BACKGROUND: Apoptosis is a mode of the death of neurocyte in hypoxic-ischemic brain damage. Study in vitro indicates that the deficiency of nerve growth factor(NGF)can induce apoptosis of neurocyte.OBJECTIVE: To discuss the relationship between hypoxic-ischemic brain damage(HIBD) and apoptosis for the research of the protective reaction of NGF against HIBD to provide a theoretical gist in the application of NGF against HIBD in neonates.DESIGN: A completely randomised controlled study.SETTINGS and MATERIALS: Forty of 7-day old SD rats with a body mass from 14 to 18 g in either gender was obtained from the experimental animal center of Nanjing Medical University, which were all SPF grade animals fed in a barrier environment.INTERVENTION: HIBD model was established in all 40 rats, which were randomly allocated into two groups: HIBD model control group ( n = 20) and NGF treatment group( n = 20), of which the animals were treated with NGF immediately after hypoxic-ischemia through abdominal cavity injection.MAIN OUTCOME MEASURES: The impact of NGF on the increase of body mass, mortality rate and the mass of the left and right brain were observed as well as the impact on apoptosis after hypoxic-ischemia by in situ nick end labelling(TUNEL) method.RESULTS: The increase of body mass in the rats of NGF treatment group was significantly higher than that of control group(P ＜ 0.01), while the mortality rate during the study of treatment group was significantly lower than that of control group. The brain mass of NGF group was similar to that of the healthy side(right side) of control group but the left side of treatment group (0. 57±0.02) g] was significantly heavier than that of control group (0. 42 ±0. 01) g] (P ＜ 0. 01 ) . There was no significant difference of brain mass between left and right side in treatment group but there was significant difference of brain mass between left and right side in control group ( P ＜ 0.01) . The apoptotic features of apoptotic positive cells found in TUNEL staining were shrinking cell body, nuclear pyrosis, nuclear fragmentation and the formation apoptotic body. The number of positive cell in NGF group was significanfiy less than that of control group( P ＜ 0.01).CONCLUSION: NGF treatment can alleviate encephalatrophy and apoptosis after hypoxic-ischemia.