碱性成纤维细胞生长因子与孤独症谱系障碍的关联
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摘要
目的了解孤独症患儿血液中碱性成纤维细胞生长因子(FGF2)水平及其与行为表现的关联性,为孤独症的病因研究提供证据。方法收集2015年9月至2017年9月在哈尔滨医科大学儿童发育行为研究中心及黑龙江省残疾人孤独症定点康复机构进行康复训练的ASD患儿40名作为病例组,哈尔滨幼儿园41名健康儿童为对照组,应用酶联免疫吸附试验(ELISA)方法检测血浆中FGF2水平。采用儿童孤独症行为量表(ABC)、儿童孤独症评定量表(CARS)、皮博迪图片词汇测验(PPVT)等量表评估孤独症患儿的严重程度及智力水平。结果 ASD患儿血液中FGF2水平(4.95 pg/mL)与正常儿童(8.51 pg/mL)差异无统计学意义(P>0.05),但在4岁年龄组中,ASD患儿(1.99 pg/mL)与对照儿童(6.82 pg/mL)的FGF2水平差异有统计学意义(P<0.05)。不同严重程度ASD患儿的FGF2水平差异有统计学意义(P<0.05);不同智商水平的ASD患儿体内FGF2水平差异有统计学意义(P<0.05)。结论孤独症患儿的FGF2水平可能存在异常,且与孤独症的严重程度及智力水平存在关联性。
Objective To investigate the level of human blood basic fibroblast growth factor(FGF2) among children with autism spectrum disorder(ASD) and its correlation with behavioral phenotypes, to provide a reference for etiological research of ASD. Methods ASD Children were selected to get rehabitation training in reseach center of children development behavior in Harbin Medical University and the rehabitation constitution for ASD disabilities in Heilongjiang, 40 children were induded as ASD group, 41 healthy children in Harbin kindergarten was classified as control group. The Autism Behavior Checklist(ABC), Childhood Autism Rating Scale(CARS) and Peabody Picture Vocabulary Test(PPVT) were used to assess the severity and intelligence of ASD children, respectively. Results No difference was found in FGF2 level between ASD children(4.95 pg/mL) and normal children(8.51 pg/mL)(P>0.05). However, difference in FGF2 level between the two groups were found in 4-year-old group(P<0.05). The level of FGF2 differed across different severity and intelligence of ASD children(P<0.05). Conclusion Abnormal levels of FGF2 in ASD children may correlate with severity of autistic traits and intelligence of children.
Objective To investigate the level of human blood basic fibroblast growth factor(FGF2) among children with autism spectrum disorder(ASD) and its correlation with behavioral phenotypes, to provide a reference for etiological research of ASD. Methods ASD Children were selected to get rehabitation training in reseach center of children development behavior in Harbin Medical University and the rehabitation constitution for ASD disabilities in Heilongjiang, 40 children were induded as ASD group, 41 healthy children in Harbin kindergarten was classified as control group. The Autism Behavior Checklist(ABC), Childhood Autism Rating Scale(CARS) and Peabody Picture Vocabulary Test(PPVT) were used to assess the severity and intelligence of ASD children, respectively. Results No difference was found in FGF2 level between ASD children(4.95 pg/mL) and normal children(8.51 pg/mL)(P>0.05). However, difference in FGF2 level between the two groups were found in 4-year-old group(P<0.05). The level of FGF2 differed across different severity and intelligence of ASD children(P<0.05). Conclusion Abnormal levels of FGF2 in ASD children may correlate with severity of autistic traits and intelligence of children.
引文
[1] ABRAHAMS B,GESCHIND D.Advances in autism genetics:on the threshold of a new neurobiology[J].Nat Rev Genet,2008,9(5):341-355.
[2] ZOGHBI H Y,BEAR M F.Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities[J].Cold Spring Harb Perspect Biol,2012,4(3).doi:10.1101/cshperspecta009886.
[3] 武丽杰.孤独症谱系障碍及其康复教育需求[J].中国学校卫生,2016,37(6):801-804.
[4] CHEN Y,RODGERS J,MCCONACHIE H.Restricted and repetitive behaviours,sensory processing and cognitive style in children with autism spectrum disorders[J].J Autism Dev Disord,2009,39(4):635-642.
[5] 武丽杰.孤独症谱系障碍儿童家庭疾病负担的现状与思考[J].中国学校卫生,2018,39(3):321-324.
[6] ITOH N.The Fgf families in humans,mice,and zebrafish:their evolutional processes and roles in development,metabolism,and disease[J].Biol Pharm Bull,2007,30(10):1819-1825.
[7] GHOSH A,GREENHERG M.Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis[J].Neuron,1995,15(1):89-103.
[8] WOODBURY M,IKEZU T.Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration[J].J Neuroimmune Pharmacol,2014,9(2):92-101.
[9] FORD-PERRISS M,ABUD H,MURPHY M.Fibroblast growth factors in the developing central nervous system[J].Clin Exp Pharmacol Physiol,2001,28(7):493-503.
[10] FUMAGALI F,BEDOGNI F,SLOTKIN T,et al.Prenatal stress elicits regionally selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress[J].Neurobiol Dis,2005,20(3):731-737.
[11] GAUGHRAN F,PAYNE J,SEDGWICK P,et al.Hippocampal FGF-2 and FGFR1 mRNA expression in major depression,schizophrenia and bipolar disorder[J].Brain Res Bull,2006,70(3):221-227.
[12] IWATA T,HEVNER R.Fibroblast growth factor signaling in development of the cerebral cortex[J].Dev Growth Differ,2009,51(3):299-323.
[13] DONO R,TEXIDO G,DUSSEL R,et al.Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice[J].EMBO J,1998,17(15):4213-4225.
[14] VACCARINO F,GRIGORENKO E,SMITH K,et al.Regulation of cerebral cortical size and neuron number by fibroblast growth factors:implications for autism[J].J Autism Dev Disord,2009,39(3):511-520.
[15] DEGUCHI Y,NAITO T,YUGE T,et al.Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor[J].Pharm Res,2000,17(1):63-69.
[16] DEGUCHI Y,OKUTSU H,OKURA T,et al.Internalization of basic fibroblast growth factor at the mouse blood-brain barrier involves perlecan,a heparan sulfate proteoglycan[J].J Neurochem,2002,83(2):381-389.
[17] EAVES R,MILNER B.The criterion-related validity of the childhood autism rating scale and the autism behavior checklist[J].J Abnorm Child Psychol,1993,21(5):481-491.
[18] 卢建平,杨志伟,舒明耀,等.儿童孤独症量表评定的信度、效度分析[J].中国现代医学杂志,2004,14(13):119-121,123.
[19] MARTELETO M,PEDROMNICO M.Validity of Autism Behavior Checklist(ABC):preliminary study[J].Revista Brasileira De Psiquiatria,2005,27(4):295-301.
[20] 马俊红,郭延庆,贾美香,等.异常行为量表中文版在儿童孤独症群体中的信效度[J].中国心理卫生杂志,2011,25(1):14-19.
[21] WEBER A,FERNALD L,GALASSO E,et al.Performance of a receptive language test among young children in Madagascar[J].PLoS One,2015,10(4):e0121767.
[22] 桑标,缪小春.皮博迪图片词汇测验修订版(PPVT—R)上海市区试用常模的修订[J].心理科学通讯,1990(5):22-27,65-67.
[23] 孙艺,梁爽,孙彩虹,等.孤独症谱系障碍患儿血清叶酸及其代谢产物与维生素B12水平状况[J].中国学校卫生,2018,39(3):331-334.
[24] THISSE B,THISSE C.Functions and regulations of fibroblast growth factor signaling during embryonic development[J].Dev Biol,2005,287(2):390-402.
[25] GUILLEMOT F,ZIMMER C.From cradle to grave:the multiple roles of fibroblast growth factors in neural development[J].Neuron,2011,71(4):574-588.
[26] RABALLO R,RHEE J,LYN-COOK R,et al.Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex[J].J Neurosc,2000,20(13):5012-5023.
[27] SZEBENYI G,DENT E W,CALLAWAY J L,et al.Fibroblast growth factor-2 promotes axon branching of cortical neurons by influencing morphology and behavior of the primary growth cone[J].J Neurosc,2001,21(11):3932-3941.
[28] SACCO R,GABRIELE S,PERSICO A M.Head circumference and brain size in autism spectrum disorder:a systematic review and meta-analysis[J].Psychiatry Res,2015,234(2):239-251.
[29] ESNAFOGLU E,AYYILDIZ S N.Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder[J].Psychiatry Res,2017,257:79-83.
[2] ZOGHBI H Y,BEAR M F.Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities[J].Cold Spring Harb Perspect Biol,2012,4(3).doi:10.1101/cshperspecta009886.
[3] 武丽杰.孤独症谱系障碍及其康复教育需求[J].中国学校卫生,2016,37(6):801-804.
[4] CHEN Y,RODGERS J,MCCONACHIE H.Restricted and repetitive behaviours,sensory processing and cognitive style in children with autism spectrum disorders[J].J Autism Dev Disord,2009,39(4):635-642.
[5] 武丽杰.孤独症谱系障碍儿童家庭疾病负担的现状与思考[J].中国学校卫生,2018,39(3):321-324.
[6] ITOH N.The Fgf families in humans,mice,and zebrafish:their evolutional processes and roles in development,metabolism,and disease[J].Biol Pharm Bull,2007,30(10):1819-1825.
[7] GHOSH A,GREENHERG M.Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis[J].Neuron,1995,15(1):89-103.
[8] WOODBURY M,IKEZU T.Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration[J].J Neuroimmune Pharmacol,2014,9(2):92-101.
[9] FORD-PERRISS M,ABUD H,MURPHY M.Fibroblast growth factors in the developing central nervous system[J].Clin Exp Pharmacol Physiol,2001,28(7):493-503.
[10] FUMAGALI F,BEDOGNI F,SLOTKIN T,et al.Prenatal stress elicits regionally selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress[J].Neurobiol Dis,2005,20(3):731-737.
[11] GAUGHRAN F,PAYNE J,SEDGWICK P,et al.Hippocampal FGF-2 and FGFR1 mRNA expression in major depression,schizophrenia and bipolar disorder[J].Brain Res Bull,2006,70(3):221-227.
[12] IWATA T,HEVNER R.Fibroblast growth factor signaling in development of the cerebral cortex[J].Dev Growth Differ,2009,51(3):299-323.
[13] DONO R,TEXIDO G,DUSSEL R,et al.Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice[J].EMBO J,1998,17(15):4213-4225.
[14] VACCARINO F,GRIGORENKO E,SMITH K,et al.Regulation of cerebral cortical size and neuron number by fibroblast growth factors:implications for autism[J].J Autism Dev Disord,2009,39(3):511-520.
[15] DEGUCHI Y,NAITO T,YUGE T,et al.Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor[J].Pharm Res,2000,17(1):63-69.
[16] DEGUCHI Y,OKUTSU H,OKURA T,et al.Internalization of basic fibroblast growth factor at the mouse blood-brain barrier involves perlecan,a heparan sulfate proteoglycan[J].J Neurochem,2002,83(2):381-389.
[17] EAVES R,MILNER B.The criterion-related validity of the childhood autism rating scale and the autism behavior checklist[J].J Abnorm Child Psychol,1993,21(5):481-491.
[18] 卢建平,杨志伟,舒明耀,等.儿童孤独症量表评定的信度、效度分析[J].中国现代医学杂志,2004,14(13):119-121,123.
[19] MARTELETO M,PEDROMNICO M.Validity of Autism Behavior Checklist(ABC):preliminary study[J].Revista Brasileira De Psiquiatria,2005,27(4):295-301.
[20] 马俊红,郭延庆,贾美香,等.异常行为量表中文版在儿童孤独症群体中的信效度[J].中国心理卫生杂志,2011,25(1):14-19.
[21] WEBER A,FERNALD L,GALASSO E,et al.Performance of a receptive language test among young children in Madagascar[J].PLoS One,2015,10(4):e0121767.
[22] 桑标,缪小春.皮博迪图片词汇测验修订版(PPVT—R)上海市区试用常模的修订[J].心理科学通讯,1990(5):22-27,65-67.
[23] 孙艺,梁爽,孙彩虹,等.孤独症谱系障碍患儿血清叶酸及其代谢产物与维生素B12水平状况[J].中国学校卫生,2018,39(3):331-334.
[24] THISSE B,THISSE C.Functions and regulations of fibroblast growth factor signaling during embryonic development[J].Dev Biol,2005,287(2):390-402.
[25] GUILLEMOT F,ZIMMER C.From cradle to grave:the multiple roles of fibroblast growth factors in neural development[J].Neuron,2011,71(4):574-588.
[26] RABALLO R,RHEE J,LYN-COOK R,et al.Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex[J].J Neurosc,2000,20(13):5012-5023.
[27] SZEBENYI G,DENT E W,CALLAWAY J L,et al.Fibroblast growth factor-2 promotes axon branching of cortical neurons by influencing morphology and behavior of the primary growth cone[J].J Neurosc,2001,21(11):3932-3941.
[28] SACCO R,GABRIELE S,PERSICO A M.Head circumference and brain size in autism spectrum disorder:a systematic review and meta-analysis[J].Psychiatry Res,2015,234(2):239-251.
[29] ESNAFOGLU E,AYYILDIZ S N.Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder[J].Psychiatry Res,2017,257:79-83.