血清25-羟基维生素D、Th17Treg细胞失衡与新生儿缺氧缺血性脑病预后的相关性研究.docx

血清25-羟基维生素D、Thl7Treg细胞失衡与新生儿缺氧缺血性脑病预后的相关性研究屈菊梅，张龙，刘荣*陕西省延安市人民医院新生儿科，陕西延安716000摘要：目的探究缺氧缺血性脑病(HlE)患儿血清25-羟基维生素D(25(OH)D)及Thl7Treg细胞的水平，并分析25(OH)D及Thl7Treg细胞与预后关系:方法选取2019年1月-2021年1月本院收治的HIE患儿79例为研究对象(HlE组)，对HlE患儿进行临床分度，分为中度46例，重度33例；选取同时期本院健康新生儿79例为对照组。利用流式细胞术检测外周血中Treg细胞比率、Th17细胞比率并计算ThlThl7细胞比率；采用酶联免疫吸附(ELISA)法检测血清中25(0H)D、白细胞介素(IL)-17和IL-23及IL-Io和转化生长因子-(TGF-)水平。根据随访的HlE患儿神经发育情况，分为神经发育正常组52例和不良神经发育组27例。采用COX法分析影响HIE患儿预后不良的因素,结果与对照组相比，HIE组血清中IL-17(62.19±6.48)ng/Lvs(38.08±4.37)ngL>IL-23(23.10±3.55)ng/Lvs(12.85±2.46)ng/L水平、ThI7细胞的比率(3.94±0.89)%vs(1.97±O.35)%及Thl7/Treg细胞的比率(0.58±0.16)vs(0.16±().08)较高(/=27.418、21.094、18.309、20.868,P均=0.000)，25(OH)D(29.14±6.02)ng/mLvs(45.37±9.07)ngmL.IL-IO(46.81±6.88)ng/Lvs(63.45±9.16)ng/L、TGF-水平(27.19±3.95)ng/Lvs(37.75±4.82)ng/L、Treg细胞的比率(6.21±1.15)%vs(8.95±1.46)%较低(曰3.251、12.910、15.06K13.104,P均=0.0(X)；与中度组相比,重度组血清中IL-17(71.03±7.40)ng/Lvs(55.84±5.82)ng/L、IL-23(29.83±4.75)ng/Lvs(18.27±2.81)ng/L水平、ThI7细胞的比率(4.89±1.1I)%vs(3.26±0.74)%及7/Treg细胞的比率(0.89±0.24)vs(O.35±O.1O)较高(/=10.207、12.189、7.833、13.716,P均=0.000),25(OH)D(20.59±4.25)ng/mLvs(35.27±7.29)ng/mL,IL-IO(39.16±5.75)ng/Lvs(52.29±7.69)ng/L、TGF-B水平(22.67±3.30)ng/Lvs(30.43±4.22)ng/L、Treg细胞的比率(4.53±0.84)%vs(7.42±l.37)%较低(/=10.362,8.282、8.803、10.745,P均=O.(XX);与中度组相比，HIE重度组入院时、治疗14d后的NBNA评分(25.61±L91)分VS(27.84±1.86)分、(34.08±1.16)分VS(36.62+1.24)分较低(/=6.050、9.222,P均=0.000)。与神经发育正常组相比，不良神经发育组入院时、治疗14d后的NBNA(25.27±1.88)分VS(27.76±1.85)分、(32.5O±l.l1)分VS(37.15±1.26)分评分较低(/=5.643、16.182,P侬0.000):与神经发育正常组相比，不良神经发育组血清中IL-17(84.04±8.76)ng/Lvs(50.84±5.30)ng/L、IL-23(35.44±5.37)ng/Lvs(I6.69±2.57)ng/L水平、Thl7细胞的比率(5.33±1.21)%vs(3.22±0.73)%及Th17/Treg细胞的比率(1.13±0.31)VS(0.29±0.08)较高(/=20.977X21.042、9.663、18.488,P均=0.000),25(OH)D(13.49±2.79)ng/mLvs(37.26±7.69)ng/mL、IL-IO(29.62±4.36)ng/Lvs(55.73±8.l9)ng/L、TGF-水平(22.93±333)ng/Lvs(39.93±5.80)ng/L、Treg细胞的比率(3.58±O.67)%vs(7.58±1.4l)%较低(/=15.500、15.437、14.048、13.916,P均=0.0)。多因素CoX分析显示，低水平25(0H)D、Thl7/Treg细胞失衡是影响HlE患儿不良预后的危险因素(HR=2.459,HR=2.425,P<0.05)三结论HIE患儿血清25(0H)D呈低表达，外周血单个核细胞Thl7rreg细胞存在免疫失衡，25(0H)D缺乏和Thl7/Treg细胞失衡可能影响HIE预后不良发生Il关键词,新生儿缺氧缺血性脑病：25-羟基维生素D；ThI7/Treg细胞中图分类号：R722.1文献标志码：ARelationshipbetweenserum25-hydroxyvitaminD,Th17/TregcellimbalanceandprognosisofneonatalhypoxicischemicencephalopathyQUJu-mei,ZHANGlong.LIURong*DepartmentofNeonatology,Yan'anPeople'sHospital.Shaafixi76000,ChinaAbstract:ObjectiveToinvestigatethelevelsof25-hydroxyvitaminD25(OH)DinserumandThl7/Tregcellsinchildrenwithhypoxic-ischemicencephalopathy(HIE),andtoanalyzetherelationshipbetween25(OH)D.Thl7/Tregcellsandprognosis.MethodsAtotalof79casesofHIEinourhospitalfromJanuary2019toJanuary2021wereselectedastheresearchobjects(HIEgroup),accordingtotheclinicalclassificationofHIEchildren,theyweredividedintomoderate46casesandsevere33cases;79casesofhealthynewbornsinourhospitalatthesametimewereselectedasthecontrolgroup.TheratiosofTregcellsandTh17cellsinperipheralbloodweredetectedbyflowcytometry,andtheratioofThlZThl7cellswascalculated;thelevelsof25(OH)D,Interleukin(IL)-17,IL-23,IL-10andtransforminggrowthfoctor-(TGF-)inserumweredetectedbyenzyme-linkedimmunosorbentassay(ELISA).Accordingtothefbllow-upneurodevelopmentalstatusofHIEchildren.HlEchildrenweredividedintoneurodeVelopmentalIynormalgroup(52cases)andadverseneurodevelopmentalgroup(27cases).COXmethodwasusedtoanalyzethefactorsaffectingtheprognosisofHIEchildren.ResultsComparedwiththoseinthecontrolgroup,thelevelsofIL-17(62.19±6.48)ng/Lvs(38.08±4.37)ngLandIL-23(23.10+3.55)ng/Lvs(12.85±2.46)ngLinserum,theratioofThl7cells(3.94±0.89)%vs(1.97±0.35)%andtheratioofThl7Tregcells(0.58±0.16)vs(0.16±0.08)inHIEgroupwerehigher(r=27.418,21.094,18.309,20.868,allP=0.000).whilethelevelsof25(OH)D(29.14±6.02)ng/mLvs(45.37+9.07)ngmL,IL-10(46.81±6.88)ng/Lvs(63.45+9.16)ng/L,TGF-(27.19±3.95)ng/Lvs(37.75±4.82)ng/LJinserumandtheratioofTregcells(6.21±1.15)%vs(8.95÷1.46)%werelower(r=13.251,12.910,15.061,13.104,allP=0.000);comparedwiththoseinthemoderategroup,thelevelsofIL-17(71.03±7.40)ng/Lvs(55.84±5.82)ng/LJandIL-23(29.83±4.75)ng/Lvs(18.27±2.81)ng/Linserum,theratioofThl7cellsI(4.89±l.ll)%vs(3.26±0.74)%andtheratioofThl7Tregcells(0.89±0.24)vs(0.35±0.10)Jintheseveregroupwerelower(/=10.207,12.189,7.833,13.716,allP=0.000),whilethelevelsof25(OH)D1(20.59+4.25)ng/mLvs(35.27±7.29)ngmL,IL-10(39.16±5.75)ng/Lvs(52.29±7.69)ngL,TGF-(22.67+3.30)ng/Lvs(30.43+4.22)ng/LinserumandtheratioofTregcells(4.53±0.84)%vs(7.42±1.37)%werehigher(/=10.362,8.282,8.803,10.745,allP=0.000);comparedwiththemoderategroup,theNBNAscoreofthesevereHIEgroupatadmission(25.61±1.91)scorevs(27.84+1.86)scoreand14daysaftertreatment(34.08±1.16)scorevs(36.62±1.24)scorewaslower(t=6.050.9.222,allP=0.000).Comparedwiththenormalneurodevelopmentgroup,thepoorneurodevelopmentgrouphadlowerNBNAscoresonadmission(25.27±1.88)scorevs(27.76±1.85)scoreand14daysaftertreatment(32.50±l.lI)scorevs(37.15±1.26)score(/=5.643,16.182,allP=0.000);comparedwith