朱萍;李德亮;张伟业;

• 1:南阳市中心医院

摘要(Abstract)：

目的观察重组人促红细胞生成素治疗新生儿缺氧缺血性脑病的疗效及对患儿生长发育的影响。方法 50例新生儿缺氧缺血性脑病患儿随机分为试验组及对照组各25例,2组患儿自出生当日起予以对症支持的常规治疗,在常规治疗基础上,试验组于第3天给予重组人促红细胞生成素400 IU/kg,每周3次,连续4周。治疗后第7天、第14天及第28天分别对2组患儿进行新生儿行为神经测定评分,并于治疗后3个月进行智能发育测试,观察患儿神经行为发育的变化。结果试验组第7天、第14天及第28天的新生儿行为神经测定评分(分别为32.4±1.32、36.3±1.47、37.7±1.81)均明显高于对照组(分别为30.5±1.56、34.8±2.14、36.1±2.03),差异有统计学意义(t=2.885、3.483、2.933,P<0.01)。治疗后3个月试验组智能发育指数(MDI)、运动发育指数(PDI)评分均高于对照组(MDI分别为76%、36%;PDI分别为72%、28%),差异有统计学意义(Z=17.286,P<0.05)。结论重组人促红细胞生成素能提高缺氧缺血性脑病患儿行为神经测定及智能发育测试评分,具有神经保护和恢复作用,对缺氧缺血性脑病患儿的近期治疗效果显著,有利于患儿的远期预后。

关键词(KeyWords)： 新生儿缺氧缺血性脑病;重组人促红细胞生成素;神经保护;生长发育

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 朱萍;李德亮;张伟业;

Email:

DOI:

参考文献(References)：

• [1] GUNN A J,THORESEN M.Chapter 10-Neonatal encephalopathy and hypoxic-ischemic encephalopathy[J].Handbook Clin Neurol,2019,162:217-237.DOI:10.1016/B978-0-444-64029-1.00010-2.
• [2] BARROIS M,PATKAI J,DELORME P,et al.Factors associated with neonatal hypoxic ischemic encephalopathy in infants with an umbilical artery pH less than 7.00[J].Eur J Obstet Gyn R B,2019,236:69-74.DOI:10.1016/j.ejogrb.2019.02.009.
• [3] 李爱丽.新生儿缺氧缺血性脑病脑动脉血流动力学变化及对预后的影响[J].中国实用神经疾病杂志,2018,21(10):49-53.DOI:10.12083/SYSJ.2018.10.270.
• [4] NEVALAINEN P,METS?RANTA M,TOIVIAINEN-SALO S,et al.Neonatal neuroimaging and neurophysiology predict infantile onset epilepsy after perinatal hypoxic ischemic encephalopathy[J].Seizure-EUR J Epilep,2020,80:249-256.DOI:10.1016/j.seizure.2020.07.002.
• [5] CHEN S,LIU X,MEI Y,et al.Early identification of neonatal mild hypoxic-ischemic encephalopathy by amide proton transfer magnetic resonance imaging:A pilot study[J].Eur J Radiol,2019,119:1-7.DOI:10.1016/j.ejrad.2019.07.021.
• [6] BASU S K,OTTOLINI K,GOVINDAN V,et al.Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy[J].J Pediatr-US,2018,203:137-143.DOI:10.1016/j.jpeds.2018.07.041.
• [7] OHKI A,SAITO S,HATA J,et al.Neurite orientation dispersion and density imaging for evaluating the severity of neonatal hypoxic-ischemic encephalopathy in rats[J].Magn Reson Imaging,2019,62:214-219.DOI:10.1016/j.mri.2019.07.013.
• [8] LAREN J M,HOLMES G L,BERG M T.Functional connectivity in term neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia[J].Pediatr Neurol,2019,94:74-79.DOI:10.1016/j.pediatrneurol.2019.01.006.
• [9] PERRONE S,WEISS M D,PROIETTI F,et al.Identification of a panel of cytokines in neonates with hypoxic ischemic encephalopathy treated with hypothermia[J].Cytokine,2018,111:119-124.DOI:10.1016/j.cyto.2018.08.011.
• [10] DIXON K,SMITH S.In neonates with hypoxic ischemic encephalopathy,is therapeutic hypothermia outside of current criteria safe?A literature review[J].J Perinat Neonat Nur,2019,25(2):54-60.DOI:10.1016/j.jnn.2018.10.005.
• [11] HERRERA T I,EDWARDS L,MALCOLM W F,et al.Outcomes of preterm infants treated with hypothermia for hypoxic-ischemic encephalopathy[J].Early Hum Dev,2018,125:1-7.DOI:10.1016/j.earlhumdev.2018.08.003.
• [12] ADAMíKOVá J,WL?NIEWSKI ?,MOLNáR T,et al.Selection of adsorbents for recombinant human erythropoietin purification[J].Sep Purif Technol,2019,228:1-8.DOI:10.1016/j.seppur.2019.115761.
• [13] SCHWARZ H,ZHANG Y,ZHAN C J,et al.Small-scale bioreactor supports high density HEK293 cell perfusion culture for the production of recombinant Erythropoietin[J].J Biotechnol,2020,309:44-52.DOI:10.1016/j.jbiotec.2019.12.017.
• [14] ZHU L,BAI X,WANG S,HU Y,et al.Recombinant human erythropoietin augments angiogenic responses in a neonatal rat model of cerebral unilateral hypoxia-ischemia[J].Neonatology,2014,106(2):143-148.DOI:10.1159/000362262.
• [15] RANGARAJAN V,JUUL S E.Erythropoietin:emerging role of erythropoietin in neonatal neuroprotection[J].Pediatr Neurol,2014,51(4):481-488.DOI:10.1016/j.pediatrneurol.2014.06.008.
• [16] FAUCHèRE J C,KOLLER B M,TSCHOPP A,Dame C,et al.Safety of Early High-Dose Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants[J].J Pediatr,2015,167(1):52.e1-3-57.e1-3.DOI:10.1016/j.jpeds.2015.02.052.
• [17] WASSINK G,DAVIDSON J O,DHILLON S K,et al.Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy[J].Curr Neurol Neurosci Rep,2019,19(2):2.DOI:10.1007/s11910-019-0916-0.
• [18] WASSINK G,DAVIDSON J O,FRASER M,et al.Non-additive effects of adjunct erythropoietin therapy with therapeutic hypothermia after global cerebral ischaemia in near-term fetal sheep[J].J Physiol,2020,598(5):999-1015.DOI:10.1113/JP279131.
• [19] ZHU X Y,YE M Y,ZHANG A M,et al.Influence of one-year neurologic outcome of treatment on newborns with moderate and severe hypoxic-ischemic encephalopathy by rhuEP0 combined with ganglioside (GM1)[J].Eur Rev Med Pharmacol Sci,2015,19(20):3955-3960.
• [20] KITTUR F S,HUNG C Y,ZHU C S,et al.Glycoengineering tobacco plants to stably express recombinant human erythropoietin with different N-glycan profiles[J].Int J Biol Macromol,2020,157:158-169.DOI:10.1016/j.ijbiomac.2020.04.199.
• [21] HA T K,HANSEN A H,KILDEGAARD H F,et al.Knockout of sialidase and pro-apoptotic genes in Chinese hamster ovary cells enables the production of recombinant human erythropoietin in fed-batch cultures[J].Metab Eng,2020,57:182-192.DOI:10.1016/j.ymben.2019.11.008.
• [22] GHEZLOU M,MOKHTARI F,KALBASI A,et al.Aggregate Forms of Recombinant Human Erythropoietin With Different Charge Profile Substantially Impact Biological Activities[J].J Pharm Sci-US,2020,109(1):277-283.DOI:10.1016/j.xphs.2019.05.036.
• [23] BAI J,ZENG S,ZHU J,et al.The Small Molecule P7C3-A20 Exerts Neuroprotective Effects in a Hypoxic-ischemic Encephalopathy Model via Activation of PI3K/AKT/GSK3β Signaling[J].Neuroscience,2020,441:197-208.DOI:10.1016/j.neuroscience.2020.05.051.
• [24] DENG K,LI Y,XIAO M,et al.Lycium ruthenicum Murr polysaccharide protects cortical neurons against oxygen-glucose deprivation/reperfusion in neonatal hypoxic-ischemic encephalopathy[J].Int J Biol Macromol,2020,158:562-568.DOI:10.1016/j.ijbiomac.2020.04.122.
• [25] LI T,WU D,YANG Y,et al.Synthesis,pharmacological evaluation and mechanistic study of scutellarin methyl ester-4′-dipeptide conjugates for the treatment of hypoxic-ischemic encephalopathy (HIE) in rat pups[J].Bioorg Chem,2020,101:1-17.DOI:10.1016/j.bioorg.2020.103980.
• [26] KIM Y S,SUNG D K,KIM H,et al.Nose-to-brain delivery of hyaluronate-FG loop peptide conjugate for non-invasive hypoxic-ischemic encephalopathy therapy[J].J Control Release,2019,307:76-89.DOI:10.1016/j.jconrel.2019.06.021.
• [27] 王剑,徐发林.纳洛酮联合脑活素治疗新生儿缺氧缺血性脑病的疗效[J].中国实用神经疾病杂志,2018,21(5):547-550.DOI:10.12083/SYSJ.2018.05.140.
• [28] 刘景艳,录海斌.神经生长因子早期干预对HIE新生儿相关时间指标脑损伤程度及神经行为的影响[J].中国实用神经疾病杂志,2019,22(10):1093-1098.DOI:10.12083/SYSJ.2019.10.145.
• [29] BARKHUIZEN M,MECHELEN R,VERMEER M,et al.Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy[J].Behav Brain Res,2019,362:77-81.DOI:10.1016/j.bbr.2019.01.016.
• [30] NAGASHIMA T,YOKOHAMA A,NAGAI K,et al.Short-term administration of recombinant human erythropoietin decreases B cell number in human peripheral blood[J].Transfus Apher Sci,2018,57(2):208-214.DOI:10.1016/j.transci.2018.01.009.
• [31] LI Q,HAN Y,DU J,et al.Recombinant human erythropoietin protects against brain injury through blunting the mTORC1 pathway in the developing brains of rats with seizures[J].Life Sci,2018,194:15-25.DOI:10.1016/j.lfs.2017.12.014.
• [32] REZA-ZALDIVAR E E,SANDOVAL-AVILA S,GUTIéRREZ-MERCADO Y K,et al.Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease[J].Neurología,2020,35(3):147-154.DOI:10.1016/j.nrleng.2017.07.006.
• [33] El-LAHONY D M,SALEH N Y,HABIB M S,et al.The role of recombinant Human erythropoietin in neonatal anemia[J].Hematol Oncol Stem Cell Ther,2019,12:1-6.DOI:10.1016/j.hemonc.2019.08.004.