原因不明复发性流产患者血清HMGB-1、SOX-4 mRNA表达变化及意义

Expression changes of serum HMGB-1 and SOX-4 levels in patients with unexplained recurrent abortion and their clinical significance

目的探讨原因不明复发性流产(URSA)患者血清高迁移率族蛋白B1(HMGB-1)、SRY相关高迁移率族蛋白4(SOX-4)表达变化及意义。方法选择98例URSA患者(URSA组)和62例妇产科接诊的健康孕妇(对照组),采用酶联免疫吸附试验检测血清HMGB-1,实时荧光定量聚合酶连反应检测血清SOX-4 mRNA。计算外周血辅助性T细胞(Th)17、调节性T细胞(Treg)占比,Pearson分析URSA患者血清HMGB-1和SOX-4 mRNA表达与Th17占比、Treg占比、Th17/Treg值的相关性。统计URSA患者再次妊娠失败情况,分析影响URSA患者再次妊娠失败的因素以及HMGB-1和SOX-4预测URSA患者再次妊娠失败的价值。结果URSA组血清HMGB-1水平,外周血Th17占比、Th17/Treg值高于对照组(P均<0.05),SOX-4 mRNA表达、外周血Treg占比低于对照组(P均<0.05)。URSA患者血清HMGB-1水平与外周血Th17占比、Th17/Treg值呈正相关(r分别为0.512、0.628,P均<0.05),与Treg占比呈负相关(r=-0.365,P<0.05);而SOX-4 mRNA表达与外周血Th17占比、Th17/Treg值呈负相关(r分别为-0.468、-0.519,P均<0.05),与Treg占比呈正相关(r=0.502,P<0.05)。Th17/Treg高、HMGB-1高、流产3次以上是URSA患者再次妊娠失败的危险因素(P均<0.05),SOX-4高是保护因素(P<0.05)。HMGB-1、SOX-4 mRNA预测URSA不良妊娠结局的曲线下面积分别为0.787、0.757,联合预测的曲线下面积为0.912,联合预测的曲线下面积高于单独预测(P均<0.05)。结论URSA患者血清HMGB-1水平升高,SOX-4 mRNA表达降低,且与Th17/Treg失衡、再次妊娠失败有关;HMGB-1和SOX-4 mRNA联合检测有助于URSA患者再次妊娠失败情况预测。

Objective To investigate the changes of serum high-mobility group protein B1(HMGB-1)and SRY-re-lated high-mobility-group box 4(SOX4)levels in patients with unexplained recurrent abortion(URSA),and their clinical significance.Methods Ninety-eight URSA patients(URSA group)and 62 healthy pregnant women(control group)were selected.Serum HMGB-1 level was detected by enzyme-linked immunosorbent assay(ELISA)and SOX-4 expression was detected by real-time fluorescence quantitative PCR,and the proportions of peripheral blood helper T cells(Th)17 and regulatory T cells(Treg)were detected.Pearson was used to analyze the correlation between serum HMGB-1 and SOX-4 expression and Th17 proportion,Treg proportion and Th17/Treg ratio in URSA patients.The recurrent pregnancy loss of URSA patients was analyzed,and the factors affecting the recurrent pregnancy loss of URSA patients were ana-lyzed,and the value of HMGB-1 and SOX-4 in predicting the recurrent pregnancy loss of URSA patients was analyzed.Results Serum HMGB-1 level,the proportion of Th17,and Th17/Treg ratio in peripheral blood of the URSA group were higher than those of the control group(all P<0.05),and the SOX-4 mRNA expression and the proportion of Treg in periph-eral blood were lower than those in the control group(all P<0.05).Serum HMGB-1 level in URSA patients was positively correlated with the proportion of Th17 and Th17/Treg ratio in the peripheral blood(r=0.512,0.628;both P<0.05),and was negatively correlated with the proportion of Treg(r=-0.365,P<0.05).The expression of SOX-4 was negatively cor-related with the proportion of Th17 and Th17/Treg ratio in peripheral blood(r=-0.468,-0.519,respectively;both P<0.05),and was positively correlated with the proportion of Treg(r=0.502,P<0.05).High Th17/Treg ratio,high HMGB-1 and more than three miscarriages were risk factors for recurrent pregnancy loss in URSA patients(all P<0.05),and high SOX-4 was a protective factor(P<0.05).The area under the curve of HMGB-1 and SOX-4 in predicting URSA adverse pregnancy outcome was 0.787 and 0.757,respectively,and the area under the curve of them combined in predic-tion was 0.912,which was higher than that of either alone(both P<0.05).Conclusion Serum HMGB-1 level increas-es and SOX-4 expression decreases in URSA patients,which is related to Th17/Treg imbalance and recurrent pregnancy loss.The combined detection of HMGB-1 and SOX-4 is of high value in predicting recurrent pregnancy loss in patients with URSA.