S100β蛋白在脑损伤中的作用及重组人红细胞生成素的干预机制研究

Role of S100β and recombinant human erythropoietin in brain injury

目的考察S100β蛋白在新生大鼠脑损伤中的作用及重组人红细胞生成素(rhEPO)干预机制的研究。方法将2日龄SD大鼠分成3组:假手术组、缺氧缺血脑损伤(HIBD)模型组(HIBD组)和rhEPO治疗组(rhEPO组),每组40只。HIBD组和rhEPO组大鼠组均存在HIBD,rhEPO组腹腔注射rhEPO 5 000 u/(kg·次)。采用ELISA法检测大鼠出生后第3、5和7天及治疗后6和24 h,第3和7天外周血的S100β蛋白表达水平;选取2015年2月—2017年10月在大连医科大学附属二院妇产科或新生儿科确诊为脑损伤的新生儿25例,选择同期出生的健康新生儿29例为对照。脑损伤的新生儿均给予皮下注射rhEPO。采用ELISA法检测rhEPO治疗前和治疗后第3、7和14天外周血的S100β蛋白表达水平。结果 3组大鼠出生后第3、5和7天外周血S100β蛋白表达水平比较:①不同时间点的S100β蛋白表达无差异(P>0.05);②3组S100β蛋白表达无差异(P>0.05);③3组的S100β蛋白表达变化趋势无差异(P>0.05)。3组大鼠治疗后6、24 h,第3和7天外周血S100β蛋白表达比较:①不同时间点的S100β蛋白表达有差异(P <0.05);②3组的S100β蛋白表达有差异(P <0.05),rhEPO组和HIBD组较假手术组高;③3组的S100β蛋白表达变化趋势有差异(P <0.05)。两组新生儿治疗前、治疗后第3、7和14天外周血S100β蛋白表达比较:①不同时间点的S100β蛋白表达有差异(P <0.05);②两组S100β蛋白表达有差异(P <0.05),脑损伤组较对照组高;③两组的S100β蛋白表达变化趋势有差异(P <0.05)。脑损伤组外周血的S100β蛋白表达呈双峰变化。对照组,轻度和重度脑损伤新生儿组治疗前、治疗后第3、7和14天外周血S100β蛋白表达比较:①不同时间点的S100β蛋白表达有差异(P <0.05);②3组的S100β蛋白表达有差异(P <0.05),重度脑损伤组较其他两组高;③3组的S100β蛋白表达变化趋势有差异(P <0.05)。轻度和重度脑损伤新生儿组外周血的S100β蛋白表达呈双峰变化。结论 S100β蛋白在新生大鼠及新生儿脑损伤可呈双峰变化,其中轻度新生儿脑损伤的S100β蛋白无双峰变化,rhEPO可用于治疗新生大鼠及新生儿脑损伤。

Objective To investigate the role of S100β protein in brain injury of the neonatal rats and potential therapeutic effect of recombinant human erythropoietin(rhEPO)on brain injury.Methods The 2-day-old SD rats were divided into the sham group,the hypoxia-ischemia brain damage group(HIBD group)and the rhEPO treatment group(rhEPO group).Rats in rhEPO group underwent intraperitoneal injection of rhEPO(5,000 U/kg).Serum S100β was measured at the 3rd d,5th d and 7th d after birth as well as 6,24,3 and 7 days after treatment.Totally 25 newborns who were admitted in our hospital from February 2015 to October 2017 due to brain injury were involved in this study.Another 29 health newborns were collected as control group.Newborns with brain injury were given rhEPO subcutaneously.Results Blood levels of S100β at different time points post birth were similar among the three groups.Circulating concentration of S100β was enhanced in HIBD group when compared with sham group,which was further enhanced with treatment of rhEPO.Expression of S100β protein in the neonatal group with brain injury was statistically significant different at various time point before and after treatment.Baby in brain injury group experienced upregulated expression of S100β compared with healthy individuals.The S100β protein expression in the neonatal group of mild and severe brain injury showed a double peak change.Neonatal subjects with severe brain injury exerted higher concentration of S100β compared with neonatal subjects with mild brain injury.Conclusions Blood concentration of S100β protein shows double peak style in both rat brain injury and neonatal brain injury.rhEPO is potentially a therapeutic option in treatment of the neonatal brain injury.