中性粒细胞明胶酶相关脂质运载蛋白在妊娠期糖尿病患者中的表达及意义
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摘要
目的:探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在妊娠期糖尿病(GDM)患者血清、脐血及胎盘组织中的表达及其与新生儿体重的相关性。方法:选取2017年6月至2017年11月于河北省人民医院产科行剖宫产术的GDM患者49例、正常妊娠(NGT组)孕妇39例。ELISA法测定母血、脐血血清NGAL水平,RT-PCR及Western blot法测定胎盘组织中NGAL mRNA及其蛋白表达。结果:GDM组母血、脐血血清NGAL水平均高于NGT组,胎盘组织中NGAL mRNA和蛋白表达量高于NGT组,两组比较差异有统计学意义(P<0.01)。NGT组和GDM组孕妇血清NGAL水平与脐血均呈正相关(r=0.399,P=0.012;r=0.349,P=0.014);GDM组孕妇血清NGAL水平与胎盘组织NGAL mRNA(r=0.848,P=0.008)、蛋白(r=0.636,P=0.011)及新生儿体重(r=0.363,P=0.014)、胰岛素抵抗指数(r=0.312,P=0.044)均呈正相关。结论:GDM患者外周血NGAL水平的增加主要可能源于胎盘组织NGAL因子的过分泌,并通过增加胰岛素抵抗(IR)参与了GDM的发生。NGAL能通过胎盘转运至胎儿并进一步影响胎儿的宫内生长发育。
Objective:To investigate the expression of neutrophil gelatinase-associated lipid carrier protein(NGAL) in serum,umbilical cord blood and placenta of gestational diabetes mellitus(GDM) and its correlation with neonatal weight.Methods:From Jun. 2017 to Nov. 2017,49 patients with GDM underwent cesarean section due to scar uterus and breech position in Hebei General Hospital and 39 age-matched normal controls were recruited.The levels of serum NGAL in maternal and umbilical blood were measured by ELISA.The expressions of NGAL mRNA and its protein in placenta tissue were detected by RT-PCR and Western blot.Results:The levels of serum NGAL in maternal and umbilical blood in GDM group were higher than those in NGT group,and the expression of NGAL mRNA and protein in placental tissue of GDM patients were higher than those in NGT group.The difference between the two groups was statistically significant(P<0.01).There was a positive correlation between maternal NGAL level and umbilical cord blood in NGT group and GDM group[(r=0.399,P=0.012)、(r=0.349,P=0.014)].The maternal NGAL level in GDM group was positively correlated with the levels of NGAL protein in placental tissue(r=0.636,P=0.011),mRNA(r=0.848,P=0.008),neonatal weight(r=0.363,P=0.014)and insulin resistance index(r=0.312,P=0.044).Conclusions: The increase of NGAL level in peripheral blood of GDM patients may be mainly due to the over-secretion of NGAL factor in placenta,and may participate in the development of GDM by increasing insulin resistance.NGAL can be transported through the placenta to the fetus and further affects the fetal intrauterine growth and development.
Objective:To investigate the expression of neutrophil gelatinase-associated lipid carrier protein(NGAL) in serum,umbilical cord blood and placenta of gestational diabetes mellitus(GDM) and its correlation with neonatal weight.Methods:From Jun. 2017 to Nov. 2017,49 patients with GDM underwent cesarean section due to scar uterus and breech position in Hebei General Hospital and 39 age-matched normal controls were recruited.The levels of serum NGAL in maternal and umbilical blood were measured by ELISA.The expressions of NGAL mRNA and its protein in placenta tissue were detected by RT-PCR and Western blot.Results:The levels of serum NGAL in maternal and umbilical blood in GDM group were higher than those in NGT group,and the expression of NGAL mRNA and protein in placental tissue of GDM patients were higher than those in NGT group.The difference between the two groups was statistically significant(P<0.01).There was a positive correlation between maternal NGAL level and umbilical cord blood in NGT group and GDM group[(r=0.399,P=0.012)、(r=0.349,P=0.014)].The maternal NGAL level in GDM group was positively correlated with the levels of NGAL protein in placental tissue(r=0.636,P=0.011),mRNA(r=0.848,P=0.008),neonatal weight(r=0.363,P=0.014)and insulin resistance index(r=0.312,P=0.044).Conclusions: The increase of NGAL level in peripheral blood of GDM patients may be mainly due to the over-secretion of NGAL factor in placenta,and may participate in the development of GDM by increasing insulin resistance.NGAL can be transported through the placenta to the fetus and further affects the fetal intrauterine growth and development.
引文
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[18] 廖灿.染色体微阵列分析技术在产前诊断中的应用[J].中华围产医学杂志,2014,17(12):804-808
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[20] Manvelyan M,Riegel M,Santos M,et al.Supernumerary marker chromosome 15 in a male with azoospermia and open bite deformity[J].Asian J Androl,2009,11(5):617-622
[21] 钟福春,兰风华,张晓林,等.一例BP3:BP3重排inv dup(1 5)的临床表型和遗传学分析[J].中华医学遗传学杂,2017,34(3):402-405
[22] 李小燕,陈倩,谢华,等.15q11.2-13.2微重复四倍体综合征1例并文献复习[J].中国循证儿科杂志,2015,10(4):292-296[22] Dennis NR,Veltman MWM,Thompson R,et al.Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13[J].Am J Med Genet,2006,140(5):434-441
[2] Makoff AJ,Flomen RH.Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi,Angelman,and inv dup(15) syndromes[J].Genome Biol,2007,8(6):R114
[3] Donlon TA,Lalande M,Wyman A,et al.Isolation of molecular probes associated with the chromosome 15 instablity in the Prader-Willi syndrome[J].Proc Natl Acad Sci USA,1986,83(12):4408-4412
[4] Battaglia A.The inv dup (15) or idic (15) syndrome (Tetrasomy 15q)[J].Orphanet J Rare Dis,2008,3:30
[5] Lalande M.Parental imprinting and human disease[J].Ann RevGenet,1996,30:173-195
[6] Browne CE,Dennis NR,Maher E,et al.Inherited interstitial duplications of proximal 15q:genotype-phenotype correlations[J].Am J Hum Genet,1997,61(6):1342-1352
[7] Crolla JA,Harvey JF,Sitch FL,et al.Supernumerary marker 15 chromosomes:a clinical,molecular and FISH approach to diagnosis and prognosis[J].Hum Genet,1995,95(2):161-170
[8] Cheng SD,Spinner NB,Zackai EH,et al.Cytogenetic and molecular characterization of inverted duplicated chromosomes 15 from 11 patients[J].Am J Hum Genet,1994,55(4):753-759
[9] 涂向东,丛学文,曾健,等.四例男性不育患者的15q11额外小标记染色体分析[J].中华医学遗传学杂志,2013,30(5):539-543
[10] Hou JW,Wang TR.Unusual features in children with inv dup(15) supernumerary marker:a study of genotype-phenotype correlation in Taiwan[J].Eur J Pediatr,1998,157(2):122-127
[11] Robinson WP,Binkert F,Gine R,et al.Clinical and molecular analysis of five inv dup (15) patients[J].Eur J Hum Genet,1993,1(1):37-50
[12] Blennow E,Nielsen KB,Telenius H,et al.Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization[J].Am J Med Genet,1995,55(1):85-94
[13] Battaglia A,Gurrieri F,Bertini E,et al.The inv dup(15) syndrome:a clinically recognizable syndrome with altered behaviour,mental retardation and epilepsy[J].Neurology,1997,48(4):1081-1086
[14] Gillberg C,Steffenburg S,Wahlstrom J,et al.Autism associated with marker chromosome[J].J Am Acad Child Adolesc Psychiat,1991,30(3):489-494
[15] Battaglia A.The inv dup(15) or idic(15) syndrome:a clinically recognisable neurogenetic disorder[J].Brain Devel,2005,27(5):365-369
[16] South ST,Lee C,Lamb AN,et al.ACMG Standards and Guidelines for constitutional cytogenomic micriarray analysis,including postnatal and prenatal applications:revision 2013[J].Genet Med,2013,15(11):901-909
[17] 吴星,朱湘玉,张颖,等.85例生长受限胎儿染色体微阵列检测结果分析[J].中华围产医学杂志,2017,20 (11):809-815
[18] 廖灿.染色体微阵列分析技术在产前诊断中的应用[J].中华围产医学杂志,2014,17(12):804-808
[19] Urraca N1,Cleary J,Brewer V,et al.The interstitial duplication 15q11.2-q13 syndrome includes autism,mild facial anomalies and a characteristic EEG signature[J].Autism Res,2013,6(4):268-279
[20] Manvelyan M,Riegel M,Santos M,et al.Supernumerary marker chromosome 15 in a male with azoospermia and open bite deformity[J].Asian J Androl,2009,11(5):617-622
[21] 钟福春,兰风华,张晓林,等.一例BP3:BP3重排inv dup(1 5)的临床表型和遗传学分析[J].中华医学遗传学杂,2017,34(3):402-405
[22] 李小燕,陈倩,谢华,等.15q11.2-13.2微重复四倍体综合征1例并文献复习[J].中国循证儿科杂志,2015,10(4):292-296[22] Dennis NR,Veltman MWM,Thompson R,et al.Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13[J].Am J Med Genet,2006,140(5):434-441
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