神经保护剂辅助亚低温对缺氧缺血性脑病患儿疗效及实验室指标的影响

Effect of neuroprotective agent assisted with mild hypothermia on curative efficacy and laboratory indexes of hypoxic-ischemic encephalopathy children

目的观察重组人促红素注射液(RHEI)辅助亚低温治疗对缺氧缺血性脑病(HIE)患儿临床疗效及安全性的影响.方法选择2015年1月至2017年12月在石家庄市第一医院接受治疗的HIE患儿110例.以采用常规治疗的55例患儿为西医常规治疗组;另外采用亚低温联合RHEI治疗的55例患儿为亚低温联合RHEI组.两组均治疗14 d,并随访10个月.比较两组患儿神经行为、智力发育指数(MDI)、精神运动发育指数(PDI)、髓鞘碱性蛋白(MBP)、S100B蛋白、神经元特异性烯醇化酶(NSE)、神经生长因子(NGF)、脑源性神经营养因子(BDNF)、胰岛素生长因子1(IGF-1)和生长激素(GH)以及临床疗效的差异,并观察不良反应发生情况.结果两组治疗后行为神经测定(NBNA)评分(分)、MDI评分(分)、PDI评分(分)、NGF(μg/L)、BDNF(ng/L)、IGF-1(pg/L)、GH(pg/L)均较治疗前升高(西医常规治疗组分别为33.72±3.19比26.81±2.38、78.95±5.51比 71.39±4.24、79.62±4.93 比 71.84±4.15、123.74±22.98 比 104.29±15.36,1 518.35±174.92 比 1 197.28± 148.43,38.25±4.96比23.16±2.87,39.27±5.24比20.97±3.15;亚低温联合RHEI组分别为39.82±3.36比 26.78±2.35、84.13±6.29 比 71.34±4.27、85.26±5.74 比 71.88±4.13、145.28±27.52 比 104.72±15.41、1 925.71±204.37 比 1 192.61±150.26、57.94±6.62 比 23.13±2.91、56.43±7.14 比 20.94±3.17),NSE(μg/L)、MBP(μg/L)、S100B(μg/L)蛋白均较治疗前降低(西医常规治疗组分别为:17.05±2.26比24.96±2.83、9.71±1.85比23.14±3.37、0.93±0.12比1.49±0.24;亚低温联合RHEI组分别为:12.48±1.94比25.03±2.81、5.48±1.42比23.17±3.35、0.61±0.07比1.51±0.25),且治疗后亚低温联合RHEI组各指标的变化较对照组更显著〔NBNA评分(分):39.82±3.36比33.72±3.19,MDI评分(分):84.13±6.29比78.95±5.51,PDI评分(分):85.26±5.74比79.62±4.93,NSE(μg/L):12.48±1.94比17.05±2.26,MBP(μg/L):5.48±1.42比9.71±1.85,S100B蛋白(μg/L):0.61±0.07比0.93±0.12,NGF(μg/L):145.28±27.52比123.74±22.98,BDNF(ng/L):1 925.71±204.37比1 518.35± 174.92,IGF-1(pg/L):57.94±6.62比38.25±4.96,GH(pg/L):56.43±7.14比39.27±5.24,均P<0.05〕.亚低温联合RHEI组总有效率明显高于西医常规治疗组〔94.55%(52/55)比81.82%(45/55),P<0.05〕.两组均无不良反应发生.结论RHEI辅助亚低温疗法可明显提高HIE患儿的临床疗效,升高NBNA、MDI、PDI评分,减轻患儿脑损伤程度,改善神经功能.

Objective To observe the effect of recombinant human erythropoietin injection(RHEI)assisted with mild hypothermia on the clinical efficacy and safety of children with hypoxic-ischemic encephalopathy(HIE).Methods From January 2015 to December 2017,110 children with HIE were treated in Shijiazhuang No.1 Hospital.Fifty-five children with routine treatment were taken as Western medicine routine treatment group.In addition,55 children treated with mild hypothermia combined with RHEI were taken as mild hypothermia+RHEI group.Both groups were treated for 14 days and followed up for 10 months.The neonatal behavioral neurological assessment(NBNA)score,mental development index(MDI),psychomotor development index(PDI),myelin basic protein(MBP),S100B protein and neuron specific enolization enzyme(NSE),nerve growth factor(NGF),brain derived neurotrophic factor(BDNF),insulin growth factor-1(IGF-1),growth hormone(GH),and differences in clinical efficacy in two groups were compared,and the occurrence of adverse reactions was observed.Results The NBNA,MDI,PDI,NGF(μg/L),BDNF(ng/L),IGF-1(pg/L),and GH(pg/L)of two groups after treatment were higher than those before treatment(the Western medicine routine treatment group:33.72±3.19 vs.26.81±2.38,78.95±5.51 vs.71.39±4.24,79.62±4.93 vs.71.84±4.15,123.74±22.98 vs.104.29±15.36,1518.35±174.92 vs.1197.28±148.43,38.25±4.96 vs.23.16±2.87,39.27±5.24 vs.20.97±3.15;the mild hypothermia+RHEI group:39.82±3.36 vs.26.78±2.53,84.13±6.29 vs.71.34±4.27,85.26±5.74 vs.71.88±4.13,145.28±27.52 vs.104.72±15.41,1925.71±204.37 vs.1192.61±150.26,57.94±6.62 vs.23.13±2.91,56.43±7.14 vs.20.94±3.17),NSE(μg/L),MBP(μg/L)and S100B(μg/L)were lower than those before treatment(the Western medicine routine treatment group:17.05±2.26 vs.24.96±2.83,9.71±1.85 vs.23.14±3.37,0.93±0.12 vs.1.49±0.24;the mild hypothermia+RHEI group:12.48±1.94 vs.25.03±2.81,5.48±1.42 vs.23.17±3.35,0.61±0.07 vs.1.51±0.25).After treatment,the changes of each index in the mild hypothermia+RHEI group were more significant than those in the control group[NABA:39.82±3.36 vs.33.72±3.19,MDI:84.13±6.29 vs.78.95±5.51,PDI:85.26±5.74 vs.79.62±4.93,NSE(μg/L):12.48±1.94 vs.17.05±2.26,MBP(μg/L):5.48±1.42 vs.9.71±1.85,S100B(μg/L):0.61±0.07 vs.0.93±0.12,NGF(μg/L):145.28±27.52 vs.123.74±22.98,BDNF(ng/L):1925.71±204.37 vs.1518.35±174.92,IGF-1(pg/L):57.94±6.62 vs.38.25±4.96,GH(pg/L):56.43±7.14 vs.39.27±5.24,all P<0.05].The total effective rate of mild hypothermia+RHEI group was significantly higher than that of Western medicine routine treatment group[94.55%(52/55)vs.81.82%(45/55),P<0.05].There were no serious adverse reactions in the two groups.Conclusion RHEI assisted with mild hypothermia therapy can significantly improve the clinical efficacy and NBNA,MDI,PDI scores of HIE children,reduce the degree of brain injury,and improve the neurological function,with good safety.