外源性神经生长因子早期干预对减轻重度窒息新生儿脑损伤程度的临床研究

Effects of early therapeutic intervention with nerve growth factor on brain damage following severe asphyxia in neonates

目的探讨外源性神经生长因子(NGF)早期干预对重度窒息新生儿脑损伤程度及血清髓鞘碱性蛋白(MBP)和酸性钙结合蛋白S-100的影响。方法将2007年1月至2009年10月广州市儿童医院新生儿重症监护室(NICU)收治的52例重度窒息复苏后的新生儿随机分为2组:常规对照组26例,即在对症支持处理的基础上使用脑蛋白水解物(脑活素)和胞二磷胆碱治疗;治疗组26例,在常规对照组的基础上尽早(生后24h内)应用鼠NGF治疗。另取同期无窒息正常足月新生儿10例作为正常对照。观察与比较两组重度缺氧缺血性脑病(HIE)的发生率以及治疗前后血清MBP、S-100的变化并进行行为神经评分测定。结果治疗组重度HIE的发生率与常规对照组比较,差异无统计学意义(23.08%vs38.46%,χ2=1.4444,P>0.05);两组间病死率比较,差异亦无统计学意义(3.85%vs7.69%,χ2=0.0000,P>0.05)。正常足月儿生后早期血清MBP为(1.68±0.85)μg/L,S-100为(1.291±0.66)μg/L。重度窒息复苏后新生儿血清MBP、S-100均显著升高。治疗组与常规对照组比较,在生后3d及生后7～8d时,血清MBP和S-100差异均具统计学意义,前者明显低于后者。生后7～8d和14～16d的行为神经评分<35分者所占百分比,治疗组(分别为40.00%和20.00%)与常规对照组(分别为70.83%和50.00%)比较,差异均具有统计学意义(χ2=4.7055,P<0.05;χ2=4.8640,P<0.05)。结论对重度窒息的新生儿,在对症支持治疗基础上尽早使用NGF能显著减轻缺氧缺血性脑损伤程度。

Objective To investigate the effects of early therapeutic intervention with nerve growth factor （NGF） on brain damage following severe asphyxia in neonates. Methods From Jan.2007 to Oct.2009, fifty-two cases of perinatal severe asphyxia in Guangzhou Children＇s Hospital were randomly assigned to two groups： the control group （26 cases） received routine treatment（including cerebrolysin and citicoline） ; the study group （26 cases） was given NGF on the basis of routine treatment as early as possible （within twenty-four hours after birth）. The incidence of the mortality were observed; the degree of hypoxic-ischemic encephalopathy （HIE） was evaluated; and the Neonatal Behavioral Neurological Assessment （NBNA） was done in both groups. Myelin basic protein （MBP） and S-100 protein were measured dynamically by ELISA in serum from all patients. Results There was no significant difference of the incidence of severe HIE and the mortality between the study group and the control group （23.08% vs 38.46%, X^ 2= 1.4444, p 〉 0.05; 3.85% vs 7.69%, X^2= 0.0000, P 〉 0.05）. The level of blood serum MBP or S-IO0 protein in the asphyxiated newborns was higher than that of the normal term newborns. At 3d and 7 - 8d after birth, the level of blood serum MBP or S-100 protein in the study group was much lower than that in the control group. The percentage of the cases whose NBNA marks were less than 35 at 7 - 8 d and 14 ~ 16 d after birth in the study group was much lower than that in the control group （40.00% vs 70.83%,X^2= 4.7055, P 〈 0.05;20.00% vs 50.00%, X^2= 4.8640, P 〈 0.05）. Conclusion Using NGF on the basis of the routine treatment as early as possible after resuscitation can reduce markedly the severity of asphyxia-induced brain damage in neonates.