新生儿缺氧缺血性脑病血清S100B浓度的变化与临床意义
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摘要
目的:探讨新生儿缺氧缺血性脑病(HIE)患儿血清S100B水平与脑实质CT值的变化及两者之间的相关性。为临床早期诊断及评价新生儿脑损伤程度,探索HIE发病机制提供客观的依据。
方法:对30例HIE患儿与10例无出生窒息对照足月儿采用酶联免疫吸附试验(ELISA)测定血清S100B水平;采用西门子欢星型螺旋CT扫描机进行头颅CT平扫,测定脑实质CT值;同时收集临床资料。
结果:①在急性期轻度HIE组血清S100B值为0.86±0.24μg/L,中重度HIE组血清S100B值为1.78±0.33μg/L,对照组血清S100B值为0.44±0.23μg/L。三组数据间有显著统计学意义(P＜0.01)。②中重度HIE组血清S100B值在急性期明显高于轻度HIE组,差异有显著统计学意义(P＜0.01)。轻度HIE组血清S100B值在急性期明显高于对照组,差异具有显著统计学意义(P＜0.01)。③中重度HIE患儿血清中S100B值由急性期的1.78±0.33μg/L下降至恢复期的0.68±0.32μg/L,差异有显著统计学意义(P＜0.01)。轻度HIE组急性期血清S100B值由急性期的0.86±0.24μg/L,下降至恢复期时0.47±0.11μg/L,差异有显著统计学意义(P＜0.01)。④S100B与CT值的关系急性期HIE组血清S100B与CT值呈负相关关系,相关系数为-0.662(r=-0.662,P＜0.01)。
结论:①HIE患儿血清S100B浓度较非HIE患儿明显升高,说明S100B参与新生儿缺氧缺血性脑病的病理生理过程。②HIE患儿血清S100B水平变化与病情轻重及病程有密切关系,提示动态监测S100B水平变化对临床早期判断HIE患儿病情轻重程度及指导治疗有重要意义。③急性期HIE组血清S100B与CT值呈负相关关系,HIE组S100B与CT值二者结合有利于更准确地评估HIE病情。
Objective:To investigate the change of serum S100B and brain CT value in patients with HIE,as well as the variations of them.It can be used to provide the evidence in early diagnosis,evaluate the degree of brain damage and guild treatment of HIE.
Methods:We detected the level of serum S100B by ELISA in 30 HIE patients and 10 control full-term infants,CT values of all the patients were obtained with huanxing Simens type of CT meanwhile,collected the clinical information completely.
Results:①The serum level of S100B in control group was 0.44±0.23μg/L.The level of S100B in mild HIE group was 0.86±0.24μg/L whereas that of moderate-severe HIE group was 1.78±0.33μg/L in the acute period.There was significant difference among them(P＜0.01).②There was significant difference of S100B concentration between the mild HIE group and the control group during the acute period(P＜0.01).There was significant difference of S100B concentration between mild HIE group and moderate-severe HIE group during the acute period (P＜0.01).③The serum level of S100B in moderate-severe HIE group in acute period was 1.78±0.33μg/L,which dropped to 0.68±0.32μg/L in recovery period.There was significant difference between them(P＜0.01).The serum level of S100B of mild HIE group in acute period was0.86±0.24μg/L,which declined to 0.47±0.11μg/L in recovery period.There was significant difference between them(P＜0.01).④The brain CT values of the moderate and severe HIE group were lower than the mild group.With correlation analysis,negative corre- lations were founded between serum S100B and brain CT values.The correlation coefficient was -0.662.
Conclusion:①The serum level of S100B in HIE patients are higher obviously than non-HIE groups,which shows that it participates in the path physiological process of neonate hypoxic-ischemic encephalopathy.②There are close relationships between the change of S100B and the patient's condition,course of disease.It is significant to supervise the trends of S100B for judging the state of disease and directing treatment in early stage of HIE.③There are negative correlation between S100B and CT scan value,they both are useful for judging the state of disease.
方法:对30例HIE患儿与10例无出生窒息对照足月儿采用酶联免疫吸附试验(ELISA)测定血清S100B水平;采用西门子欢星型螺旋CT扫描机进行头颅CT平扫,测定脑实质CT值;同时收集临床资料。
结果:①在急性期轻度HIE组血清S100B值为0.86±0.24μg/L,中重度HIE组血清S100B值为1.78±0.33μg/L,对照组血清S100B值为0.44±0.23μg/L。三组数据间有显著统计学意义(P＜0.01)。②中重度HIE组血清S100B值在急性期明显高于轻度HIE组,差异有显著统计学意义(P＜0.01)。轻度HIE组血清S100B值在急性期明显高于对照组,差异具有显著统计学意义(P＜0.01)。③中重度HIE患儿血清中S100B值由急性期的1.78±0.33μg/L下降至恢复期的0.68±0.32μg/L,差异有显著统计学意义(P＜0.01)。轻度HIE组急性期血清S100B值由急性期的0.86±0.24μg/L,下降至恢复期时0.47±0.11μg/L,差异有显著统计学意义(P＜0.01)。④S100B与CT值的关系急性期HIE组血清S100B与CT值呈负相关关系,相关系数为-0.662(r=-0.662,P＜0.01)。
结论:①HIE患儿血清S100B浓度较非HIE患儿明显升高,说明S100B参与新生儿缺氧缺血性脑病的病理生理过程。②HIE患儿血清S100B水平变化与病情轻重及病程有密切关系,提示动态监测S100B水平变化对临床早期判断HIE患儿病情轻重程度及指导治疗有重要意义。③急性期HIE组血清S100B与CT值呈负相关关系,HIE组S100B与CT值二者结合有利于更准确地评估HIE病情。
Objective:To investigate the change of serum S100B and brain CT value in patients with HIE,as well as the variations of them.It can be used to provide the evidence in early diagnosis,evaluate the degree of brain damage and guild treatment of HIE.
Methods:We detected the level of serum S100B by ELISA in 30 HIE patients and 10 control full-term infants,CT values of all the patients were obtained with huanxing Simens type of CT meanwhile,collected the clinical information completely.
Results:①The serum level of S100B in control group was 0.44±0.23μg/L.The level of S100B in mild HIE group was 0.86±0.24μg/L whereas that of moderate-severe HIE group was 1.78±0.33μg/L in the acute period.There was significant difference among them(P＜0.01).②There was significant difference of S100B concentration between the mild HIE group and the control group during the acute period(P＜0.01).There was significant difference of S100B concentration between mild HIE group and moderate-severe HIE group during the acute period (P＜0.01).③The serum level of S100B in moderate-severe HIE group in acute period was 1.78±0.33μg/L,which dropped to 0.68±0.32μg/L in recovery period.There was significant difference between them(P＜0.01).The serum level of S100B of mild HIE group in acute period was0.86±0.24μg/L,which declined to 0.47±0.11μg/L in recovery period.There was significant difference between them(P＜0.01).④The brain CT values of the moderate and severe HIE group were lower than the mild group.With correlation analysis,negative corre- lations were founded between serum S100B and brain CT values.The correlation coefficient was -0.662.
Conclusion:①The serum level of S100B in HIE patients are higher obviously than non-HIE groups,which shows that it participates in the path physiological process of neonate hypoxic-ischemic encephalopathy.②There are close relationships between the change of S100B and the patient's condition,course of disease.It is significant to supervise the trends of S100B for judging the state of disease and directing treatment in early stage of HIE.③There are negative correlation between S100B and CT scan value,they both are useful for judging the state of disease.
引文
1.中华医学会儿科学分会新生儿学组.新生儿缺氧缺血性脑病诊断标准,中华儿科杂志,2005,43(8):584.
2.Moore BW.A soluble protein characteristic of the narvers system[J].Bioehem Biophys Res Commun,1965,19(6):739-744.
3.Buttner T,Weyers S,Postert T,et al.S100protein:a serum marker of focal brain damage after ischemic territorial MCA infarction[J].Stroke,1997,28(10):1961-1964.
4.Degirolamo P.Introduction.Microsc Ices Tech[M]2003;60:537-539.
5.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type[J].Biochimicaet Biophysica Acta(BBA)/Molecular Cell Research,1999,1450:191-231.
6.陈建魁,尹秀云等.神经生化标志物S100蛋白的分子生物学基础及临床应用.军事医学科学院院刊.,2003,27,1:70-72.
7.Sheng JG,Mark RE,Griffin WST.S100B protein expression in Alzheimer disease:potential role in the pathogeneses of neuritic plaques[J].Neurosci Res,1994,39:398-04
8.Ravasi T,Hsu K,Goyette G,et al.Probing the S100 protein family through genomic and functional analysis[J].Genomics,2004,84(1):10-22.
9o.Leal RB,Frizzo JK,Tramontina F,et al.S100B protein stimulates calcineurin activity[J].Neuro report,2004,15:317-320.
10.Goncalves DS,Lenz G,Karl J,et al.Extra cellular S100B protein modulates ERK in astrocyte cultures[J].Neuro report,2000,11:807-809.
11.Amer-wahlin,Herbst A,Lindoff C,et al.Brain-specific NSE and S100 proteins in umbilical blood after normal delivery[J].ClinicaChim Acta,2001,304:57-63.
12.Nagdyman N,Komen W,Ko H,et al.Early biochemical indicators of hypoxic-ischemic encepha lopathy after birth asphyxia[J].Pediatr Res,2001,49:502-506.
13.Hu JC,Astets F,Guevara JL,et al.S100B stimulates nitricoljdesynthase activity and mRNA leve ls in mtcortical astroeytes[J].Bid Chum,1996,271(5):2543-2547.
14.Nygaard O,Langbakk B,Rommer B.Age-and sex-related changes of S100 protein concentrati-ons in cerebrospinal fluid and serum in patients with no previou history of neurological disorder[J].Clin Chem,1997,43(3):541-543.
15.Raabe A,Seifert V.Fatal secondary increase in Serum S100B protein alter severe head injury[J]Neurosurg,1999,91(5):875.
16.Connolly ES Jr.Win_free CJ,Rampemad A,et al.Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid enderterectomy[J].Neurosurgety,2001,49(5):1076-1082.
17.Nagdyman N,Komen W,Ko H,et al.Early biochemical indicators of hypoxic ischemic encephalopathy after birth asphyxia.Pediatr Res,2001,49:502-506.
18.Thorngren-Jerneck K,Ailing C.S100 in term newborn infant with hypoxic-ischemic encephalopathy after birth asphyxia[J].Neurochem,1999,73(suppl):S198.
19.Thorngren-Jerneck K,Ailing C,Herbst A,et al.S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic-ischemic encephalopathy[J].Pediatr Res,2004,55:406-412.
20.王兴河,杨毅,秦梅等.新生鼠缺氧缺血性脑损伤S100、NSE mRNA和蛋白水平变化.中国当代儿科杂志,2002,2(6),381-385.
21.Ingerbrigtsen T,Romner B.S-100 protein serum measurements relate to early magnetic resonsnee imaging after minor headinjury.Cases report[J].Neurosurg,1996,85(5):945-948
22.Ingerbrigtsen T,Waterloo K Jacobsen EA,et al.Traumatic brain damageinminor head injury re lation of S100 protein measurements to magnetic ronance imaging and an neuro behanvioral outcome[J].Neurosurgery.1999,45(3)468-476.
23.夏黎明.出生周内正常新生儿与HIE患儿颅脑CT表现.中国医学影像学志,2000,8,(5):336338.
24.刘玉花,姜山,肖格林.新生儿HIE的CT诊断(附55例分析).实用放射学杂志.2002.18(6):514-515.
25.韩玉昆,许植之,虞人杰.新生儿缺氧缺血性脑病[M].2000,第1版,132-138.
1.Moore BW.A soluble protein characteristic of the nerves system[J].Bioehern Biophys Res Commun,1965,19(6):739-744
2.Buttner T,Weyers S,Postert T,et al.S100protein:serum marker of focal brain damage after ischemic territorial MCA infarction.Stroke,1997,28(10):1961-1964
3.Degirolamo P.Introduction.Microsc Ices Tech 2003;60:537-539.
4.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type.[J].Biochimicaet Biophysica Acta(BBA)/Molecular Cell research,1999,1450:191-231.
5.陈建魁,尹秀云等.神经生化标志物S100蛋白的分子生物学基础及临床应用.军事医学科学院院刊,2003,27,1:70-72.
6.Ravasi T,Hsu K,Goyette G,et al.Probing the S100 protein family through genomic and functional analysis[J],Genomics,2004,84(1):10-22.
7.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type[J].Biochimical Biophysica Acta(BBA)/Molecular Cell research,1999,1450:191-231.
8.Leal RB,Frizzo JK,Tramontina F,et al.S100B protein stimulates Calcineurin activity[J].Neuro report,2004,15:317-320.
9.Goncalves DS,Lenz G,Karl J,et al.Extra cellular S100B protein modulates ERK in astrocyte cultures[J].Neuro report,2000,11:807-809.
10.Amer-wahlin,Herbst A,Lindoff C,et al.Brain-specific NSE and S100 proteins in umbilical blood after normal delivery[J].ClinicaChim Acta,2001,304:57-63.
11.Nagdyman N,Komen W,Ko H,et al.Early biochemicalindicators of hypoxic-iscnemic encephalopathy after birth asphyxia.Pediatr Res,2001,49:502-506.
12.Hu J.C,Astets F,Guevara JL,et al.S100B stimulates nitric oljdesynthase activity and mRNA levels in mtcortical astroeytes.Bid Chum,1996,271(5):2543-2547.
13.Nygaard O,Langbakk B,Rommer B.Age-and sex-related changes of S100 protein concentrations in cerebrospinal fluid and serum in patients with no previou history of neurological disorder.Clin Chem,1997,43(3):541-543.
14.Raabe A,Seifert V.Fatal secondary increase in Serum S100B protein alter severe head injury[J]Neurosurg,1999,91(5):875.
15.Cormolly ES Jr,Win_free CJ,Rampemad A,et al.Serum S100Bprotein levels are correlated with subclinical neurocognitive declines after carotid enderterectomy.Neursurgety,2001,49(5):1076-1082.
16.陈建魁,尹秀云等.神经生化标志物S100蛋白的分子生物学基础及临床应用.军事医学科学院院刊,2003,27,1:70-72.
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18.Spinella PC,Dominguez T,Drott H,et al.S100[beta]protein serum levels in healthy children and its association with outcomein pediatric traumatic brain injury[J].Cirt Care Med,2003,31:939-945.
19.徐卫平,谢飞,雷恩奇等.ELISA检测S100B蛋白方法的建立与临床应用.上海免疫学杂志,2002,22(2):119-120.
20.曾鸿毅,邹劲涛,苏亮等.宫内窒息新生儿的脐血S100B蛋白检测的临床意义.放射免疫学杂志,2007,20(4):364-365.
21.Takahasli M,Chamczuka,Hong Y et al.Rapid and Sensitive imrnunoassay for the measurement of serum S100B using isoform specific monoclonal antibody.Clin Chem,1999,45(8):1307-1311.
22.Wiesmann M,Missler U,Grottmann D,etal.Peasma S100B protein concentration in healthy adults in age-and sex-independent.Clin Chem,1998,44(5):1056-1057.
23.Nagdyman N,Komen W,Ko H,et al.Early biochemical indicators of hypoxic ischemic encephalopathy after birth asphyxia.Pediatr Res,2001,49:502-506.
24.Thorngren-Jerneck K,Ailing C.S100 in term newborn infant with hypoxic-ischemic encephalopathy after birth asphyxia[J].Neurochem,1999,73(suppl):S198.
25.Thorngren-Jerneck K,Ailing C,Herbst A,et al.S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic-ischemic encephalopathy[J].Pediatr Res.2004,55:406-412.
26.王兴河,杨毅,秦梅等.新生鼠缺氧缺血性脑损伤S100、NSE mRNA和蛋白水平变化.中国当代儿科杂志,2002,2(6),381-385.
27.Gazzolo D,Di Iorio R,Marinoni E,et al.S100B protein increases in asphyxiated term infants de veloping intraventricular hemorrhage[J].Crit Med,2002,30:1356-1306.
28.GazzoloD,VinesiP,Bartocci M.Elevated S100 blood level as an early indicator of intraventricular hemorrhage in preterm infants[J].NeurolSci,1999,170(1):32-35.
29.Gazzolo D,Marinoni E,Dilorio R,et al.Urinary S100B protein measurements:a tool for the early identification of hypoxic-ischemic encephalopathy in asphyxiated full-term infants[J].Crit Care Med.2004,32(1):131-136.
30.Gazzolo D,Di Iorio R,Marinoni E,et al.Circulating S100[beta]protein is increased in intrauterine growth retarded fetuses.Pediatr Res,2002,51:215-129.
31.GazzoloD,BmschettiniM,CorvinoV,et al.S100B protein concentrations in amniotic fluid are correlated with gestational age and with cerebral ultrasoun scarming parameters results in healthy fetues.Clin Chem.2001,47(5):954-956.
2.Moore BW.A soluble protein characteristic of the narvers system[J].Bioehem Biophys Res Commun,1965,19(6):739-744.
3.Buttner T,Weyers S,Postert T,et al.S100protein:a serum marker of focal brain damage after ischemic territorial MCA infarction[J].Stroke,1997,28(10):1961-1964.
4.Degirolamo P.Introduction.Microsc Ices Tech[M]2003;60:537-539.
5.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type[J].Biochimicaet Biophysica Acta(BBA)/Molecular Cell Research,1999,1450:191-231.
6.陈建魁,尹秀云等.神经生化标志物S100蛋白的分子生物学基础及临床应用.军事医学科学院院刊.,2003,27,1:70-72.
7.Sheng JG,Mark RE,Griffin WST.S100B protein expression in Alzheimer disease:potential role in the pathogeneses of neuritic plaques[J].Neurosci Res,1994,39:398-04
8.Ravasi T,Hsu K,Goyette G,et al.Probing the S100 protein family through genomic and functional analysis[J].Genomics,2004,84(1):10-22.
9o.Leal RB,Frizzo JK,Tramontina F,et al.S100B protein stimulates calcineurin activity[J].Neuro report,2004,15:317-320.
10.Goncalves DS,Lenz G,Karl J,et al.Extra cellular S100B protein modulates ERK in astrocyte cultures[J].Neuro report,2000,11:807-809.
11.Amer-wahlin,Herbst A,Lindoff C,et al.Brain-specific NSE and S100 proteins in umbilical blood after normal delivery[J].ClinicaChim Acta,2001,304:57-63.
12.Nagdyman N,Komen W,Ko H,et al.Early biochemical indicators of hypoxic-ischemic encepha lopathy after birth asphyxia[J].Pediatr Res,2001,49:502-506.
13.Hu JC,Astets F,Guevara JL,et al.S100B stimulates nitricoljdesynthase activity and mRNA leve ls in mtcortical astroeytes[J].Bid Chum,1996,271(5):2543-2547.
14.Nygaard O,Langbakk B,Rommer B.Age-and sex-related changes of S100 protein concentrati-ons in cerebrospinal fluid and serum in patients with no previou history of neurological disorder[J].Clin Chem,1997,43(3):541-543.
15.Raabe A,Seifert V.Fatal secondary increase in Serum S100B protein alter severe head injury[J]Neurosurg,1999,91(5):875.
16.Connolly ES Jr.Win_free CJ,Rampemad A,et al.Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid enderterectomy[J].Neurosurgety,2001,49(5):1076-1082.
17.Nagdyman N,Komen W,Ko H,et al.Early biochemical indicators of hypoxic ischemic encephalopathy after birth asphyxia.Pediatr Res,2001,49:502-506.
18.Thorngren-Jerneck K,Ailing C.S100 in term newborn infant with hypoxic-ischemic encephalopathy after birth asphyxia[J].Neurochem,1999,73(suppl):S198.
19.Thorngren-Jerneck K,Ailing C,Herbst A,et al.S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic-ischemic encephalopathy[J].Pediatr Res,2004,55:406-412.
20.王兴河,杨毅,秦梅等.新生鼠缺氧缺血性脑损伤S100、NSE mRNA和蛋白水平变化.中国当代儿科杂志,2002,2(6),381-385.
21.Ingerbrigtsen T,Romner B.S-100 protein serum measurements relate to early magnetic resonsnee imaging after minor headinjury.Cases report[J].Neurosurg,1996,85(5):945-948
22.Ingerbrigtsen T,Waterloo K Jacobsen EA,et al.Traumatic brain damageinminor head injury re lation of S100 protein measurements to magnetic ronance imaging and an neuro behanvioral outcome[J].Neurosurgery.1999,45(3)468-476.
23.夏黎明.出生周内正常新生儿与HIE患儿颅脑CT表现.中国医学影像学志,2000,8,(5):336338.
24.刘玉花,姜山,肖格林.新生儿HIE的CT诊断(附55例分析).实用放射学杂志.2002.18(6):514-515.
25.韩玉昆,许植之,虞人杰.新生儿缺氧缺血性脑病[M].2000,第1版,132-138.
1.Moore BW.A soluble protein characteristic of the nerves system[J].Bioehern Biophys Res Commun,1965,19(6):739-744
2.Buttner T,Weyers S,Postert T,et al.S100protein:serum marker of focal brain damage after ischemic territorial MCA infarction.Stroke,1997,28(10):1961-1964
3.Degirolamo P.Introduction.Microsc Ices Tech 2003;60:537-539.
4.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type.[J].Biochimicaet Biophysica Acta(BBA)/Molecular Cell research,1999,1450:191-231.
5.陈建魁,尹秀云等.神经生化标志物S100蛋白的分子生物学基础及临床应用.军事医学科学院院刊,2003,27,1:70-72.
6.Ravasi T,Hsu K,Goyette G,et al.Probing the S100 protein family through genomic and functional analysis[J],Genomics,2004,84(1):10-22.
7.Donato R.Functional roles of S100 protein,calcium-binding proteins of the EF-hand type[J].Biochimical Biophysica Acta(BBA)/Molecular Cell research,1999,1450:191-231.
8.Leal RB,Frizzo JK,Tramontina F,et al.S100B protein stimulates Calcineurin activity[J].Neuro report,2004,15:317-320.
9.Goncalves DS,Lenz G,Karl J,et al.Extra cellular S100B protein modulates ERK in astrocyte cultures[J].Neuro report,2000,11:807-809.
10.Amer-wahlin,Herbst A,Lindoff C,et al.Brain-specific NSE and S100 proteins in umbilical blood after normal delivery[J].ClinicaChim Acta,2001,304:57-63.
11.Nagdyman N,Komen W,Ko H,et al.Early biochemicalindicators of hypoxic-iscnemic encephalopathy after birth asphyxia.Pediatr Res,2001,49:502-506.
12.Hu J.C,Astets F,Guevara JL,et al.S100B stimulates nitric oljdesynthase activity and mRNA levels in mtcortical astroeytes.Bid Chum,1996,271(5):2543-2547.
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