IL-35对重度子痫前期孕妇血清诱导的脐静脉内皮细胞凋亡的作用
- Author:
- No author available
- Journal Title:
- Chinese Journal of Obstetrics and Gynecology
- Issue:
- 8
- DOI:
- 10.3760/cma.j.issn.0529-567x.2019.08.009
- Key Word:
- No keyword available
Abstract： 目的 探讨白细胞介素35(IL-35)对子痫前期(PE)孕妇外周血血清诱导的脐静脉内皮细胞(HUVEC)凋亡的作用.方法 收集2016年9月至2018年3月在江苏省滨海县人民医院确诊的重度PE孕妇22例(重度PE组)、轻度PE孕妇24例(轻度PE组),同期24例正常孕妇为对照组,检测3组孕妇的外周血中IL-35水平及诱导型调节性T淋巴细胞35(iTr35)细胞的比例.并于体外分离培养正常孕妇分娩的健康新生儿脐带的HUVEC.(1)分为空白对照组、重度PE血清组和IL-35+重度PE血清组,流式细胞仪检测3组HUVEC的凋亡率;(2)分为空白对照组、肿瘤坏死因子α(TNF-α)组和IL-35+TNF-α组,基因芯片法检测3组HUVEC基因的表达水平;(3)分为空白对照组、TNF-α组、TNF-α+IL-35组、TNF-α+IL-35+shRNA组和TNF-α+IL-35+对照RNA组,实时荧光定量PCR技术和蛋白印迹法检测5组HUVEC中表达水平差异最大的基因;(4)分为空白对照组、重度PE血清组、IL-35+重度PE血清组、IL-35+重度PE血清+shRNA组和IL-35+重度PE血清+对照RNA组,采用2',7'-二氯荧光黄双乙酸盐法和荧光亲脂性羰花青染料法检测5组HUVEC中活性氧簇水平和线粒体膜电位水平.结果 (1)重度PE组[1.56 μg/L(0.40～2.01 μg/L)]和轻度PE组[2.83 μg/L(1.85～4.11μg/L)]孕妇的外周血IL-35水平与对照组孕妇比较[4.14 μg/L(2.14～6.93 μg/L)],差异有统计学意义(P＜0.05).重度PE组[0.82％(0.43％～1.54％)]和轻度PE组[1.23％(0.46％～2.03％)]孕妇的外周血iTr35细胞的比例与对照组[1.64％(0.88％～2.43％)]孕妇比较,差异有统计学意义(P＜0.05).(2)体外培养HUVEC,与空白对照组及TNF-α组细胞比较,IL-35+TNF-α组细胞上调倍数最大的基因是S100A8;与空白对照组[6.01％(3.46％～9.54％)]细胞比较,重度PE血清组[16.43％ (6.25％～22.32％)]细胞的凋亡率显著增加,差异有统计学意义(P＜0.05);与重度PE血清组比较,IL-35+重度PE血清组细胞的凋亡率[分别为16.43％(6.25％～22.32％),10.34％(5.89％～14.56％)]、活性氧簇水平(分别为133.1±2.2、50.2±3.0)均降低,线粒体膜电位水平(分别为0.21±0.11、5.12±0.24)增加,差异均有统计学意义(P均＜0.05).结论 PE孕妇外周血IL-35水平和iTr35细胞的比例均降低,与PE孕妇血管内皮细胞损伤相关.
- [1]钱中清,李新萍,王才智,等.重度子痫前期患者血清对人脐静脉血管内皮细胞的氧化性损伤研究[J].2013,(3).
- [2]李留霞,李秀芳,张兰兰,等.子痫前期孕妇血浆对人脐静脉内皮细胞增殖和凋亡的影响及其与溶血磷脂酸受体的关系[J].2013,(2).
- [3]Jian, Shen,Yu, Zhu,Kaiyuan, Huang,etc.Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells.[J].2016.
- [4]Babbette LaMarca,Denise C. Cornelius,Ashlyn C. Harmon,etc.Identifying immune mechanisms mediating the hypertension during preeclampsia[J].2016,311(1 Pt.2).
- [5]Ikemoto M,Otsuka K,Terasaki F.Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network.[J].2009,11(3).
- [6]Kate E, Duhig,Andrew H, Shennan.Recent advances in the diagnosis and management of pre-eclampsia.[J].2015,7.
- [7]Sha, Xiaojin,Meng, Shu,Li, Xinyuan,etc.Interleukin-35 Inhibits Endothelial Cell Activation by Suppressing MAPK-AP-1 Pathway[J].2015,290(31).
- [8]Yanhui, Ma,Lei, Chen,Guohua, Xie,etc.Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3.[J].2016,(45).
- [9]Schneider F,Andriantsitohaina R,Meziani F,etc.Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility.[J].2006,169(4).
- [10]Jelmer R. Prins,Hendrik M. Boelens,Janneke Heimweg.Preeclampsia is Associated with Lower Percentages of Regulatory T Cells in Maternal Blood[J].2009,28(3).
- [11]Collison LW,Chaturvedi V,Henderson AL,etc.IL-35-mediated induction of a potent regulatory T cell population.[J].2010,11(12).
- [12]Ozkan,Z.S.,Simsek,M.,Ilhan,F.,etc.Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease[J].2014,27(15).
- [13]Tranquilli,A.L.,Dekker,G.,Magee,L.,etc.The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP[J].2014,4(2).
- [14]Weiping Cao,Xinzhi Wang,Tinmei Chen,etc.The Expression of Notch/Notch Ligand, IL-35, IL-17, and Th17/Treg in Preeclampsia[J].2015,2015(1).
- [15]Babbette LaMarca,Denise Cornelius,Kedra Wallace.Elucidating Immune Mechanisms Causing Hypertension During Pregnancy[J].2013,28(Jul.).
- [16]Cornelius, Denise C.,LaMarca, Babbette,Harmon, Ashlyn C.,etc.The role of inflammation in the pathology of preeclampsia[J].2016,130(5).
- [17]Hsu K,Endoh Y,Geczy CL,etc.S100A8 modulates mast cell function and suppresses eosinophil migration in acute asthma.[J].2011,14(9).
- [18]Lissette C, Sánchez-Aranguren,Carlos E, Prada,Carlos E, Ria?o-Medina,etc.Endothelial dysfunction and preeclampsia: role of oxidative stress.[J].2014,5.