子痫前期孕妇血清代谢组学分析
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摘要
目的:比较妊娠子痫前期(PE)患者分娩前后血清代谢轮廓的变化,建立疾病区分模型并筛选出具有潜在临床应用价值的特征代谢物。方法:选取2017年9月—2018年3月天津市第三中心医院收入院的孕妇共45例,其中PE患者(PE组)20例,正常孕妇(对照组)25例,应用超高效液相色谱与质谱联用仪(UPLC-MS)分别检测PE组孕妇分娩前、分娩后以及对照组的血清标本,筛选出差异性特征代谢物并进行分析。结果:构建了妊娠PE组血清代谢轮廓模型,共筛选出溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6、14-甲基十六烷酸、二十二酸和1,25-二羟基维生素D3-26,23内酯共5种差异性代谢产物,且溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6和14-甲基十六烷酸3种物质在PE分娩前与分娩后的差异有统计学意义(均P<0.05)。结论:构建代谢轮廓模型具有很强地区分PE患者分娩前后及正常孕妇的能力,筛选出特征代谢物能够反映PE患者代谢水平的变化趋势,为PE的预测、诊治提供参考。
Objective:To study the changes of serum metabolic profile before and after pregnancy in pre-eclampsia, to establish a disease differentiation model and to screen out characteristic metabolites with potential clinical diagnostic value.Methods: The subjects were 20 cases of eclampsia(group PE)(44.4%) and 25 normal pregnant women(group Control)(55.6%)from September 2017 to March 2018. All the serum samples were analyzed by using the ultra performance liquid chromatography-mass spectra(UPLC-MS). Based on the multivariate statistical analysis method of pattern recognition, we analyzed the experimental data and analyzed the trend of the differential characteristic metabolites. Results: The serum metabolic profile principal component analysis model( PCA) and the orthogonal partial least square( OPLS-DA) discriminant model of the pregnancy eclampsia group were constructed. At the same time, 5 kinds of characteristic metabolites in the serum of the patients with eclampsia were screened and identified. They are LysoPC(18:0), LysoPC(22:6),(S)-14-Methylhexadecanoic acid, behenic acid, 1, 25-Dihydroxyvitamin D3-26, 23-lactone. There was difference on the level of LysoPC(18:0), LysoPC(22:6) and(S)-14-Methylhexadecanoic between preoperatively and postoperatively. The difference was statistically significant( P<0.05).Conclusions: The construction of metabolic profile discriminant model has a strong ability to distinguish patients with pre-eclampsia and normal pregnant women. Screening out characteristic metabolites can reflect the state of lipid metabolism in early pre-eclampsia, and provide reference and help for the prediction, diagnosis and treatment of PE.
Objective:To study the changes of serum metabolic profile before and after pregnancy in pre-eclampsia, to establish a disease differentiation model and to screen out characteristic metabolites with potential clinical diagnostic value.Methods: The subjects were 20 cases of eclampsia(group PE)(44.4%) and 25 normal pregnant women(group Control)(55.6%)from September 2017 to March 2018. All the serum samples were analyzed by using the ultra performance liquid chromatography-mass spectra(UPLC-MS). Based on the multivariate statistical analysis method of pattern recognition, we analyzed the experimental data and analyzed the trend of the differential characteristic metabolites. Results: The serum metabolic profile principal component analysis model( PCA) and the orthogonal partial least square( OPLS-DA) discriminant model of the pregnancy eclampsia group were constructed. At the same time, 5 kinds of characteristic metabolites in the serum of the patients with eclampsia were screened and identified. They are LysoPC(18:0), LysoPC(22:6),(S)-14-Methylhexadecanoic acid, behenic acid, 1, 25-Dihydroxyvitamin D3-26, 23-lactone. There was difference on the level of LysoPC(18:0), LysoPC(22:6) and(S)-14-Methylhexadecanoic between preoperatively and postoperatively. The difference was statistically significant( P<0.05).Conclusions: The construction of metabolic profile discriminant model has a strong ability to distinguish patients with pre-eclampsia and normal pregnant women. Screening out characteristic metabolites can reflect the state of lipid metabolism in early pre-eclampsia, and provide reference and help for the prediction, diagnosis and treatment of PE.
引文
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[20]Kabarowski JH,Xu Y,Witte ON.Lysophosphatidylcholine as a ligand for immunoregulation[J].Biochem Pharmacol,2002,64(2):161-167.
[21]叶彬,陈令斌,刘融.溶血磷脂酰胆碱对MG-63细胞粘附和迁移能力的影响[J].实用癌症杂志,2016,31(10):1593-1596.
[22]Ntambi JM,Miyazaki M,Stoehr JP,et al.Loss of stearoyl-CoAdesaturase-1 function protects mice against adiposity[J].Proc Natl Acad Sci U S A,2002,99(17):11482-11486.
[23]Lager S,Jansson T,Powell TL.Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids[J].Am J Physiol Cell Physiol,2014,307(8):C738-C744.
[24]Yang C,Lim W,Bazer FW,et al.Oleic acid stimulation of motility of human extravillous trophoblast cells is mediated by stearoyl-CoAdesaturase-1 activity[J].Mol Hum Reprod,2017,23(11):755-770.
[25]Brodowski L,Burlakov J,Myerski AC,et al.Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta[J].PLoS One,2014,9(6):e98527.
[26]von Versen-Hoynck F,Brodowski L,Dechend R,et al.Vitamin Dantagonizes negative effects of preeclampsia on fetal endothelial colony forming cell number and function[J].PLoS One,2014,9(6):e98990.
[27]Abedi P,Mohaghegh Z,Afshary P,et al.The relationship of serum vitamin D with pre-eclampsia in the Iranian women[J].Matern Child Nutr,2014,10(2):206-212.
[28]Hsu P,Santner-Nanan B,Dahlstrom JE,et al.Altered decidual DC-SIGN+antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia[J].Am J Pathol,2012,181(6):2149-2160.
[29]Akbari S,Khodadadi B,Ahmadi SAY,et al.Association of vitamin Dlevel and vitamin D deficiency with risk of preeclampsia:Asystematic review and updated meta-analysis[J].Taiwan J Obstet Gynecol,2018,57(2):241-247.
[30]马亚楠,刘世国,蒋峰丽,等.维生素D受体基因多态性与子痫前期遗传易感性的关系[J].中华围产医学杂志,2015,18(6):442-445.
[2]果崇慧,杨青,赵雪莲,等.子痫前期相关危险因素的临床分析[J].河北医药,2016,38(16):2465-2467.
[3]Verlohren S,Galindo A,Schlembach D,et al.An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia[J].Am J Obstet Gynecol,2010,202(2):161.e1-161.e11.
[4]徐匆,刘伟.子痫前期胎盘学研究进展[J].中国实用妇科与产科杂志,2009,25(4):300-303.
[5]中华医学会妇产科学分会妊娠期高血压疾病学组.妊娠期高血压疾病诊治指南(2015)[J].中华妇产科杂志,2015,50(10):721-728.
[6]Feng S,Du YQ,Zhang L,et al.Analysis of serum metabolic profile by ultra-performance liquid chromatography-mass spectrometry for biomarkers discovery:application in a pilot study to discriminate patients with tuberculosis[J].Chin Med J(Engl),2015,128(2):159-168.
[7]Wang B,Chen D,Chen Y,et al.Metabonomic profiles discriminate hepatocellular carcinoma from liver cirrhosis by ultraperformance liquid chromatography-mass spectrometry[J].J Proteome Res,2012,11(2):1217-1227.
[8]宋颖,杨孜,沈洁,等.规律产前检查子痫前期患者早期临床发病特点分析[J].中国实用妇科与产科杂志,2014,30(6):457-461.
[9]Austdal M,Skr覽stad RB,Gundersen AS,et al.Metabolomic biomarkers in serum and urine in women with preeclampsia[J].PLoSOne,2014,9(3):e91923.
[10]曲光瑾,耿琳,刘雨舒,等.子痫前期的分子生物学研究进展[J].现代妇产科进展,2016,25(8):633-635.
[11]Demirci O,Tugˇrul AS,Dolgun N,et al.Serum lipids level assessed in early pregnancy and risk of pre-eclampsia[J].J Obstet Gynaecol Res,2011,37(10):1427-1432.
[12]郑敏辉,戴木森.胎盘生长因子在肺纤维化发病机制中的作用[J].中国组织工程研究与临床康复,2007,11(19);3817-3820.
[13]Mijal RS,Holzman CB,Rana S,et al.Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm delivery[J].J Matern Fetal Neonatal Med,2012,25(7):1135-1141.
[14]Taylor RN,Grimwood J,Taylor RS,et al.Longitudinal serum concentrations of placental growth factor:evidence for abnormal placental angiogenesis in pathologic pregnancies[J].Am J Obstet Gynecol,2003,188(1):177-182.
[15]贾冬丽,方丽丽,司晓辉.血清PDGF-BB、PIGF和sFlt-1水平检测在预测子痫前期发生中的意义[J].安徽医药,2018,22(4):685-688.
[16]陈雪,应豪,杨慧琳.血清PAPP-A、PIGF和sFlt-1在子痫前期患者中的表达及意义[J].医学临床研究,2015,32(7):1277-1279.
[17]童彤,程蔚蔚.胎盘微环境改变与子痫前期[J].中国实用妇科与产科杂志,2016,32(4):330-334.
[18]刘莉,叶鹏.胎盘生长因子抑制胎盘缺血引起的高血压[J].中华高血压杂志,2016,24(2):180.
[19]王莉,陈小菊,郑林媚.脂联素、MMP-9、胎盘生长因子在子痫前期患者中的表达水平及与妊娠结局相关性研究[J].中国优生与遗传杂志,2018,26(1):9-12.
[20]Kabarowski JH,Xu Y,Witte ON.Lysophosphatidylcholine as a ligand for immunoregulation[J].Biochem Pharmacol,2002,64(2):161-167.
[21]叶彬,陈令斌,刘融.溶血磷脂酰胆碱对MG-63细胞粘附和迁移能力的影响[J].实用癌症杂志,2016,31(10):1593-1596.
[22]Ntambi JM,Miyazaki M,Stoehr JP,et al.Loss of stearoyl-CoAdesaturase-1 function protects mice against adiposity[J].Proc Natl Acad Sci U S A,2002,99(17):11482-11486.
[23]Lager S,Jansson T,Powell TL.Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids[J].Am J Physiol Cell Physiol,2014,307(8):C738-C744.
[24]Yang C,Lim W,Bazer FW,et al.Oleic acid stimulation of motility of human extravillous trophoblast cells is mediated by stearoyl-CoAdesaturase-1 activity[J].Mol Hum Reprod,2017,23(11):755-770.
[25]Brodowski L,Burlakov J,Myerski AC,et al.Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta[J].PLoS One,2014,9(6):e98527.
[26]von Versen-Hoynck F,Brodowski L,Dechend R,et al.Vitamin Dantagonizes negative effects of preeclampsia on fetal endothelial colony forming cell number and function[J].PLoS One,2014,9(6):e98990.
[27]Abedi P,Mohaghegh Z,Afshary P,et al.The relationship of serum vitamin D with pre-eclampsia in the Iranian women[J].Matern Child Nutr,2014,10(2):206-212.
[28]Hsu P,Santner-Nanan B,Dahlstrom JE,et al.Altered decidual DC-SIGN+antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia[J].Am J Pathol,2012,181(6):2149-2160.
[29]Akbari S,Khodadadi B,Ahmadi SAY,et al.Association of vitamin Dlevel and vitamin D deficiency with risk of preeclampsia:Asystematic review and updated meta-analysis[J].Taiwan J Obstet Gynecol,2018,57(2):241-247.
[30]马亚楠,刘世国,蒋峰丽,等.维生素D受体基因多态性与子痫前期遗传易感性的关系[J].中华围产医学杂志,2015,18(6):442-445.