摘要
目的比较宫内生长受限（IUGR）新生儿与适于胎龄儿（AGA）代谢物的差异，了解IUGR患儿代谢物变化，探讨其组织器官损伤可能的代谢机制，为临床干预提供依据。方法以2009年7月至2015年6月在中国人民解放陆军总医院八一儿童医院NICU住院、并接受代谢疾病筛查的45例IUGR患儿和56例AGA新生儿为研究对象，比较其外周静脉血中21种氨基酸和55种肉碱含量的差异，以及游离肉碱和酰基肉碱与总肉碱的比值变化。结果1．不同出生体质量（〈第3百分位、第3百分位-〈第5百分位、第5百分位-〈第10百分位、第10百分位-第90百分位）比较中体质量〈第3百分位的IUGR患儿外周血丙氨酸（F=2．94，P=0．03）、同型半胱氨酸（F=3．83，P=0．01）、蛋氨酸（F=2．88，P=0．04）、鸟氨酸（F=3．32，P=0．02）、丝氨酸（F=3．09，P=0．03）、酪氨酸（F=4．76，P=0．00）明显低于AGA新生儿，体质量第3百分位-〈第5百分位IUGR患儿外周血中的差异性氨基酸呈代偿性增加，且高于AGA新生儿。2．不同胎龄新生儿之间存在差异性代谢物：早产儿外周静脉血丙氨酸（t=2．423，P=0．026）、脯氨酸（t=2．470，P=0．023）、十四碳二酰肉碱（t=-2．870，P=0．010）水平高于足月儿，而二十六碳酰肉碱（t=-2．189，P=0．041）水平明显低于足月儿；AGA早产新生儿外周静脉血丙氨酸（t=2．354，P=0．022）、谷氨酰胺（t=2．520，P=0．015）、六氢吡啶羧酸（t=2．017，P=0．049）、脯氨酸（t=2．204，P=0．032）水平明显高于AGA足月儿，而同型半胱氨酸（t=-2．624，P=0．011）、庚酰肉碱（t=-2．403，P=0．020）、葵二酰肉碱（t=-5．739，P=0．000）水平明显低于AGA足月儿；IUGR早产儿外周静脉血同型半胱氨酸（t=-2．421，P=0．020）、癸酰肉碱（t=-2．181，P=0．035）、甲基丙二酰肉碱（t=-2．373，P=0．022）、戊二酰肉碱（t=-2．165，P：0．036）、癸二酰肉碱（t=-4．148，P=0．000）、羟基乙酰肉碱（t=-2．097，P=0．042）、羟基十六烯酰肉碱（t=-2．446，P=0．019）水平明显高于IUGR足月儿，而精氨酸（t=2．167，P=0．036）、谷氨酸（t=2．469，P=0．018）、组氨酸（t=2．718，P=0．009）、亮氨酸异亮氨酸（t=3．938，P=0．000）、鸟氨酸（t=4．264，P=0．000）、丝氨酸（t=2．647，P=0．011）、苏氨酸（t=2．311，P=0．026）、色氨酸（t=4．040，P=0．000）、缬氨酸（t=2．700，P=0．01）、庚酰肉碱（t=-2．441，P=0．019）、十八碳二烯肉碱（t=2．449，P=0．018）水平明显低于IUGR足月儿。3．不同性别AGA新生儿之间未发现差异性代谢物（P〉0．05），但不同性别IUGR患儿间存在差异性代谢产物，其中男性IUGR患儿天冬氨酸（t=2．521，P=0．016）、谷氨酸（t=-2．175，P=0．035）水平均低于女性IUGR患儿；而男性IUGR患儿二十六碳烯酸水平高于女性IUGR患儿（t=2．231，P=0．031）。4．出生体质量对新生儿体内游离肉碱的水平以及游离肉碱和酰基肉碱与总肉碱的比值无明显影响（P均〉0．05）。结论IUGR对胎儿-新生儿血浆氨基酸和酰基肉碱代谢有明显影响，对出生体质量〈第3百分位者影响最明显；随着出生体质量增加，氨基酸和酰基肉碱呈代偿性增加或减低，至体质量达第10百分位时，上述变化可达到或接近ACA新生水平。
Objective To compare the differences in metabolites between newborns with intrauterine growth restriction （IUGR） and appropriate for gestational age （AGA） in order to understand the changes in metabolites of newborns with IUGR and explore the possible metabolic mechanism of tissue and organ damages in patients with IUGR, with the ultimate goal of providing the basis for clinical intervention. Methods A total of 45 newborns with IUGR and 56 AGA newborns who were hospitalized in the Neonatal Intensive Care Unit of Bayi Children＇s Hospital, the General Hospital of the Chinese People＇s Liberation Army between July 2009 and June 2015 and who underwent metabolic disease screening were enrolled in this study. The differences in of 21 amino acids and 55 carnitines in peripheral blood, as well as the changes in the ratios of free carnitine and acylcarnitine to total camitine, were compared. Results （ 1 ） According to the comparison of birth weights （ 〈 3rd percentile ,3rd - 〈 5th percentile ,5th - 〈 10th percentile, and 10th -90th percentile）,peripheral blood of the IUGR newborns with birth weight 〈 3rd percentile contained lower con centrations of alanine （ F = 2.94, P =- 0.03 ）, homocysteine （ F = 3.83, P = 0.01 ） , methionine （ F = 2.88, P = 0.04 ） , ornithine （ F = 3.32,P = 0.02）, serine （ F = 3.09,P = 0.03 ） and tyrosine （ F = 4.76, P = 0.00） than those of the AGA newborns. In the peripheral blood of the IUGR newborns with birth weight of 3rd - 〈 5th percentile, the diversity of alanine concentrations showed compensatory increase, and their alanine concentrations were higher than those of the AGA newborns. （2） Metabolites also had significant differences in different gestational age groups ： the concentrations of alanine （ t = 2. 423, P = 0.026）, proline （ t = 2. 470, P = 0. 023 ）, and 14 - carbon acylcarnitine （ t = - 2. 870, P = 0.010 ） in premature was higher than those in full - term newborns, but the concentration of 26 - carbon acylcarnitine （ t = - 2. 189, P = 0.041 ） was lower than full - term ones ; the concentrations of alanine （ t = 2. 354, P = 0.022 ）, glutamine （ t = 2. 520, P = 0.015 ）, pipecolic acid （ t = 2.017, P = 0. 049 ）, proline （ t = 2. 204, P =0. 032） in premature AGA new- borns were higher than those in full - term ones, but the concentrations of homocysteine （ t = - 2. 624, P = 0.011 ）, seven carbon acylcarnitine（ t = - 2. 403, P = 0. 020） , and ten carbon acylcarnitine （ t = - 5. 739, P = 0. 000） were lower than those of full - term AGA newborns; the concentrations of homocysteine （ t = - 2. 421, P = 0.020）, decanogl carnitine（ t = - 2. 181, P = 0. 035 ）, methyl propylene acyl carnitine （ t = - 2. 373, P = 0. 022 ）, pentyl acyl carnitine （ t = - 2.165, P = 0. 036）, decyl acyl carnitine （ t = - 4.148, P = 0. 000）, hydroxyl acetyl carnitine （ t = - 2.097, P = 0. 042）, hydroxyl cetyl acylcarnitine （t = - 2. 446, P = 0. 019） in premature IUGR were higher than those in full - term IUGR newborns ; but the concentrations of arginine （ t = 2.167, P = 0.036）, glutamic acid （ t = 2. 469, P = 0.018 ）, histidine （ t = 2.718, P = 0. 009 ）, leucine/isoleucine （ t = 3. 938, P = 0. 000 ）, ornithine （ t = 4. 264, P = 0. 000）, serine （ t = 2. 647, P = 0.011 ）, threonine （ t = 2.311, P = 0. 026 ）, tryptophan （ t = 4. 040, P = 0.000）, valine （ t = 2. 700, P = 0.01 ）, 7 - carbon acylcarnitine （ t = - 2.441, P = 0.019 ）, 18 - carbon diene carnitine （ t = 2. 449, P = 0. 018 ）, capric acylcarnitine （t = - 4. 148,P = 0.000） and hydroxyl acetyl carnitine （ t = - 2. 097, P = 0. 042 ） were lower than those in full - term IUGR newborns. （3） For AGA newborns, metabolites had no differences between male and female （P 〉 0. 05 ） ;however, for newborns with IUGR, metabolites significantly differed between male and female, and the concentrations of aspartic acid （ t = 2.521, P = 0.016 ）, glutamate （ t = - 2. 175, P = 0. 035 ） in male IUGR were lower than those in female newborns with IUGR, but the concentration of 26 -carbon carnitine （t = 2.231 ,P = 0. 031 ） was higher than that in female group. （4） Birth weight had no significant effect on free carnitine concentration or on the ratios of free carnitine and acylcarnitine to total carnitine（ all P 〉 0.05 ）. Conclusions IUGR infants exhibit significant abnormalities in amino acid and acylcarnitine metabolism, especially those with birth weight 〈 3rd percentile. With the increase of birth weight, amino acids and acylcarnitines showed compensatory increases or decrease, and when birth weight reached the 10th percentile,the newborns with IUGR were close to the AGA newborns.
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2016年第14期1066-1071,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
国家自然科学基金（81471087）
关键词
宫内生长受限
氨基酸
肉碱
酰基肉碱
代谢组
Intrauterine growth restriction
Amino acids
Carnitine
Acylcarnitine
Metabolome
作者简介
通信作者：刘敬，Email：liujingbj@sina．com
