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1、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
2、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(62.196.48)ng/Lvs(38.084.37)ngLIL-23(23.103.55)ng/Lvs(12.852.46)ng/L水平、ThI7细胞的比率(3.940.89)%vs(1.97O.35)%及Thl7/Treg细胞的比率(0.580.16)vs(0.16().08)较高(/=2
3、7.418、21.094、18.309、20.868,P均=0.000),25(OH)D(29.146.02)ng/mLvs(45.379.07)ngmL.IL-IO(46.816.88)ng/Lvs(63.459.16)ng/L、TGF-水平(27.193.95)ng/Lvs(37.754.82)ng/L、Treg细胞的比率(6.211.15)%vs(8.951.46)%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(71.037.40)ng/Lvs(55.845.82)ng/L、IL-23(29.834.75)ng/Lv
4、s(18.272.81)ng/L水平、ThI7细胞的比率(4.891.1I)%vs(3.260.74)%及7/Treg细胞的比率(0.890.24)vs(O.35O.1O)较高(/=10.207、12.189、7.833、13.716,P均=0.000),25(OH)D(20.594.25)ng/mLvs(35.277.29)ng/mL,IL-IO(39.165.75)ng/Lvs(52.297.69)ng/L、TGF-B水平(22.673.30)ng/Lvs(30.434.22)ng/L、Treg细胞的比率(4.530.84)%vs(7.42l.37)%较低(/=10.362,8.282、8
5、.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(25.61L91)分VS(27.841.86)分、(34.081.16)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(25.271.88)分VS(27.761.85)分、(32.5Ol.l1)分VS(37.151.26)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(84.048.76)ng/Lvs(50.845.30
6、)ng/L、IL-23(35.445.37)ng/Lvs(I6.692.57)ng/L水平、Thl7细胞的比率(5.331.21)%vs(3.220.73)%及Th17/Treg细胞的比率(1.130.31)VS(0.290.08)较高(/=20.977X21.042、9.663、18.488,P均=0.000),25(OH)D(13.492.79)ng/mLvs(37.267.69)ng/mL、IL-IO(29.624.36)ng/Lvs(55.738.l9)ng/L、TGF-水平(22.93333)ng/Lvs(39.935.80)ng/L、Treg细胞的比率(3.58O.67)%vs(7
7、.581.4l)%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,P0.05)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-hydrox
8、yvitaminD,Th17/TregcellimbalanceandprognosisofneonatalhypoxicischemicencephalopathyQUJu-mei,ZHANGlong.LIURong*DepartmentofNeonatology,YananPeoplesHospital.Shaafixi76000,ChinaAbstract:ObjectiveToinvestigatethelevelsof25-hydroxyvitaminD25(OH)DinserumandThl7/Tregcellsinchildrenwithhypoxic-ischemicencep
9、halopathy(HIE),andtoanalyzetherelationshipbetween25(OH)D.Thl7/Tregcellsandprognosis.MethodsAtotalof79casesofHIEinourhospitalfromJanuary2019toJanuary2021wereselectedastheresearchobjects(HIEgroup),accordingtotheclinicalclassificationofHIEchildren,theyweredividedintomoderate46casesandsevere33cases;79ca
10、sesofhealthynewbornsinourhospitalatthesametimewereselectedasthecontrolgroup.TheratiosofTregcellsandTh17cellsinperipheralbloodweredetectedbyflowcytometry,andtheratioofThlZThl7cellswascalculated;thelevelsof25(OH)D,Interleukin(IL)-17,IL-23,IL-10andtransforminggrowthfoctor-(TGF-)inserumweredetectedbyenz
11、yme-linkedimmunosorbentassay(ELISA).Accordingtothefbllow-upneurodevelopmentalstatusofHIEchildren.HlEchildrenweredividedintoneurodeVelopmentalIynormalgroup(52cases)andadverseneurodevelopmentalgroup(27cases).COXmethodwasusedtoanalyzethefactorsaffectingtheprognosisofHIEchildren.ResultsComparedwiththose
12、inthecontrolgroup,thelevelsofIL-17(62.196.48)ng/Lvs(38.084.37)ngLandIL-23(23.10+3.55)ng/Lvs(12.852.46)ngLinserum,theratioofThl7cells(3.940.89)%vs(1.970.35)%andtheratioofThl7Tregcells(0.580.16)vs(0.160.08)inHIEgroupwerehigher(r=27.418,21.094,18.309,20.868,allP=0.000).whilethelevelsof25(OH)D(29.146.02
13、)ng/mLvs(45.37+9.07)ngmL,IL-10(46.816.88)ng/Lvs(63.45+9.16)ng/L,TGF-(27.193.95)ng/Lvs(37.754.82)ng/LJinserumandtheratioofTregcells(6.211.15)%vs(8.951.46)%werelower(r=13.251,12.910,15.061,13.104,allP=0.000);comparedwiththoseinthemoderategroup,thelevelsofIL-17(71.037.40)ng/Lvs(55.845.82)ng/LJandIL-23(
14、29.834.75)ng/Lvs(18.272.81)ng/Linserum,theratioofThl7cellsI(4.89l.ll)%vs(3.260.74)%andtheratioofThl7Tregcells(0.890.24)vs(0.350.10)Jintheseveregroupwerelower(/=10.207,12.189,7.833,13.716,allP=0.000),whilethelevelsof25(OH)D1(20.59+4.25)ng/mLvs(35.277.29)ngmL,IL-10(39.165.75)ng/Lvs(52.297.69)ngL,TGF-(
15、22.67+3.30)ng/Lvs(30.43+4.22)ng/LinserumandtheratioofTregcells(4.530.84)%vs(7.421.37)%werehigher(/=10.362,8.282,8.803,10.745,allP=0.000);comparedwiththemoderategroup,theNBNAscoreofthesevereHIEgroupatadmission(25.611.91)scorevs(27.84+1.86)scoreand14daysaftertreatment(34.081.16)scorevs(36.621.24)scorewaslower(t=6.050.9.222,allP=0.000).Comparedwiththenormalneurodevelopmentgroup,thepoorneurodevelopmentgrouphadlowerNBNAscoresonadmission(25.271.88)scorevs(27.761.85)scoreand14daysaftertreatment(32.50l.lI)scorevs(37.151.26)score(/=5.643,16.182,allP=0.000);comparedwith