子痫前期胎盘中第10号染色体缺失性磷酸酶和张力蛋白同源物基因、Syncytin-1与母体内皮损伤、滋养细胞损伤的相关性

目的研究子痫前期胎盘中第10号染色体缺失性磷酸酶和张力蛋白同源物基因(phosphatase and tensin homologue-deleted chromosome ten gene,PTEN)、Syncytin-1与母体内皮损伤、滋养细胞损伤的相关性。方法选择2015年2月至2017年12月在南方医科大学附属小榄医院诊断为子痫前期并分娩的46例患者及同期正常分娩的的80名孕妇,分娩前留取母体外周血并测定内皮损伤标志物的含量,分娩后留取胎盘并测定PTEN、Syncytin-1、细胞凋亡基因的表达量以及氧化应激标志物的含量。结果子痫前期胎盘组织中PTEN的mRNA表达量显著高于正常胎盘组织(t=32.797、P<0.000),Syncytin-1的mRNA表达量显著低于正常胎盘组织(t=28.506、P<0.000);子痫前期患者母体血液循环中内皮素-1(endothelin-1,ET-1)、可溶性血管内皮生长因子受体-1(soluble fms-like tyrosine kinase receptor 1,sFlt-1)的含量显著高于正常妊娠孕妇(t值分别为39.884、40.243、P均<0.001),且与胎盘组织中PTEN的mRNA表达量呈正相关(相关系数分别为0.674、0.596,P分别为0.004、0.007),与Syncytin-1的mRNA表达量呈负相关(相关系数分别为-0.615、-0.637,P分别为0.009、0.008),一氧化氮(nitric oxide,NO)、前列腺素I 2(prostaglandin I2,PGI2)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、胎盘生长因子(Placental growth factor,PLGF)的含量显著低于正常妊娠孕妇(t值分别为30.944、27.404、32.827、26.644、P均<0.001),且与胎盘组织中PTEN的mRNA表达量呈负相关(相关系数分别为-0.648、-0.592、-0.537、-0.613,P分别为0.006、0.009、0.013、0.007),与Syncytin-1的mRNA表达量呈正相关(相关系数分别为0.632、0.572、0.537、0.654,P值分别为0.010、0.013、0.015、0.009);子痫前期胎盘组织中还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(nicotinamide adenine dinucleotide phosphate-reduced oxidase 4,NOX4)、丙二醛(malondialdehyde,MDA)、8-羟基脱氧鸟苷酸(8-hydroxydeoxyguanosine,8-OHdG)的含量以及自杀相关因子(factors associated suicide,Fas)、Fas配体(fas ligand,FasL)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)、含半胱氨酸的天冬氨酸蛋白水解酶(cysteine-containing aspartic acid proteolytic enzymes-3,Caspase-3)的mRNA表达量显著高于正常胎盘组织(t值分别为27.714、27.704、26.786、22.622、27.964、25.496、25.893、30.837、28.975、P均<0.001),且与胎盘组织中PTEN的mRNA表达量呈正相关(相关系数分别为0.703、0.651、0.593、0.628、0.449、0.552、0.612、0.569、0.502,P值分别为0.003、0.007、0.004、0.006、0.016、0.010、0.006、0.012、0.018),gn Syncytin-1的mRNA表达量呈负相关(相关系数分别为-0.615、-0.714、-0.577、-0.548、-0.512、-0.585、-0.619、-0.495、-0.662,P值分别为0.009、0.001、0.013、0.015、0.018、0.011、0.009、0.023、0.003),Peroxiredoxin-Ⅱ蛋白(PrxⅡ)、PrxⅢ、超氧化物歧化酶(superoxide dismutase,SOD)的含量以及B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)的mRNA表达量显著低于正常胎盘组织(t值分别为26.115、23.502、21.439、17.194、P均<0.001),且与胎盘组织中PTEN的mRNA表达量呈负相关(相关系数分别为-0.713、-0.657、-0.591、-0.642,P值分别为<0.001、0.006、0.009、0.007),与Syncytin-1的mRNA表达量呈正相关(相关系数分别为0.562、0.711、0.682、0.608,P值分别为0.013、<0.001、0.002、0.008)。结论子痫前期胎盘中PTEN的高表达以及Syncytin-1的低表达能够加重母体内皮损伤以及胎盘滋养细胞损伤。

Correlation between the deletion of phosphatase and tensin homolog gene on chromosome 10, syncytin-1 and the damage of maternal endothelium and trophoblast in preeclampsia placenta

Objective To study the correlation between phosphatase and tensin homolog deleted on chromosome ten(PTEN),Syncytin-1 in preeclamptic placenta and maternal endothelial injury,trophoblast injury.Methods From February 2015 to December 2017,46 patients diagnosed as preeclampsia and delivered in Xiaolan Hospital Affiliated to Southern Medical University and 80 pregnant women with normal delivery in the same period were selected.Before delivery,maternal peripheral blood was collected and the content of endothelial injury markers was determined;after delivery,the placenta was retained and the expression of PTEN,Syncytin-1,apoptosis gene and the contents of oxidative stress markers were measured.Results The mRNA expression of PTEN in placental tissue of preeclampsia was significantly higher than that of normal placental tissue(t=32.797,P<0.000),and the mRNA expression of Syncytin-1 was significantly lower than that of normal placental tissue(t=28.506,P<0.001);the content of ET-1 and sFlt-1 in the blood circulation of the maternal body of preeclampsia was significantly higher than thsoe of normal pregnant women(t=39.884,40.243;all P<0.000)and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficient=0.674,0.596;P=0.004,0.007),negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficient=-0.615,-0.637;P<0.009,0.008);the content of NO,PGI2,VEGF and PLGF were significantly lower than thse of normal pregnant women(t=30.944,27.404,32.827,26.644;all P<0.001)and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficient=-0.648,-0.592,-0.537,-0.613;P=0.006,0.009,0.013,0.007),positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficient=0.632,0.572,0.537,0.654;P<0.010,0.013,0.015,0.009);The contents of NOX4,MDA,8-OHdG and the mRNA expression of Fas,FasL,Bax,GRP78,CHOP,Caspase-3 in placental tissue of preeclampsia was significantly higher than that of normal placental tissue(t=27.714,27.704,26.786,27.964,22.622,25.496,25.893,30.837,28.975;all P<0.001)and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficient=0.703,0.651,0.593,0.628,0.449,0.552,0.612,0.569,0.502;P<0.003,0.007,0.004,0.006,0.016,0.010,0.006,0.012,0.018),negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficient=-0.615,-0.714,-0.577,-0.548,-0.512,-0.585,-0.619,-0.495,-0.662;P<0.009,0.001,0.013,0.015,0.018,0.011,0.009,0.023,0.003);The contents of PrxII,PrxIII,SOD and mRNA expression of Bcl-2 in placental tissue of preeclampsia was significantly lower than that of normal placental tissue(t=26.115,23.502,17.194;all P<0.000)and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficient=-0.713,-0.657,-0.591,-0.642;P<0.001,0.006,0.009,0.007),positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficient=0.562,0.711,0.682,0.608,P<0.013,<0.001,0.002,0.008).Conclusion The high expression of PTEN and the low expression of syncytin-1 in placenta of preeclampsia can aggravate the damage of endothelium and trophoblast.