妊娠期糖尿病171例血清热休克蛋白70、热休克转录因子1表达与妊娠结局的关系

Relationship between the expressions of HSP70 and HSF1 in 171 pregnant women with diabetes and pregnancy outcome

目的探讨妊娠期糖尿病病人(GDM)血清热休克蛋白70(HSP70)、热休克转录因子1(HSF1)的表达水平及其与妊娠结局的关系。方法选取2019年1月至2021年1月在首都医科大学大兴教学医院收治的171例GDM病人作为GDM组,根据GDM病人妊娠结局分为妊娠结局不良组(91例)和妊娠结局良好组(80例),另选取同期在该院产检的健康孕妇172例作为对照组,采用酶联免疫吸附测定(ELISA)检测血清HSP70水平,采用实时荧光定量聚合酶链反应(qRT-PCR)法测定血清HSF1 mRNA的相对表达量,比较两组实验室指标。采用Pearson法分析GDM病人血清HSP70、HSF1 mRNA水平与临床指标的相关性;使用受试者工作特征曲线(ROC曲线)分析HSP70、HSF1及超敏C-反应蛋白(hs-CRP)、胱抑素C对GDM病人发生不良妊娠结局的预测价值。结果与对照组比较,GDM组病人空腹血糖、糖化血红蛋白(HbA1c)及肌酐、尿酸、hs-CRP、胱抑素C、HSP70[(0.30±0.10)μg/L比(0.21±0.09)μg/L]、HSF1 mRNA水平(1.99±0.35比1.03±0.32)明显升高(均P<0.05);对照组发生不良妊娠结局有13例,发生率为7.56%,GDM组病人发生不良妊娠结局有91例,发生率为53.22%,GDM组病人发生不良妊娠结局发生率远高于对照组(P<0.05);与妊娠结局良好组比较,妊娠结局不良组病人血清HSP70[(0.33±0.14)μg/L比(0.27±0.05)μg/L]、HSF1 mRNA(2.22±0.30比1.73±0.41)明显升高(均P<0.05);GDM病人血清HSP70与HSF1 mRNA水平呈正相关(P<0.05),血清HSP70、HSF1 mRNA水平与空腹血糖、HbA1c、肌酐、尿酸、hs-CRP及胱抑素C均呈正相关(均P<0.05);ROC曲线分析结果表明,HSP70、HSF1、hs-CRP、胱抑素C预测GDM病人发生不良妊娠结局的曲线下面积(AUC)分别为0.62、0.69、0.60、0.58;血清HSP70联合HSF1 mRNA预测GDM病人发生不良妊娠结局的AUC为0.83,明显高于血清HSP70、HSF1 mRNA及hs-CRP、胱抑素C水平单独预测(均P<0.05)。结论GDM病人血清HSP70、HSF1呈高表达,且二者联合检测对妊娠结局具有较高的预测价值。

Objective To investigate the expression levels of serum heat shock protein 70(HSP70)and heat shock factor 1(HSF1)in patients with gestational diabetes mellitus(GDM)and their relationship with pregnancy outcome.Methods A total of 171 GDM pa-tients who were treated in Daxing Teaching Hospital of Capital Medical University from January 2019 to January 2021 were selected as the GDM group.According to the pregnancy outcomes of GDM patients,they were assigned into a poor pregnancy outcome group(n=91)and a good pregnancy outcome group(n=80),and 172 healthy pregnant women who underwent obstetric examination in the same hospital during the same period were served as the control group.The serum HSP70 level was detected by enzyme linked immunosor-bent assay(ELISA),and the relative expression of serum HSF1 mRNA was determined by real-time fluorescence quantitative PCR(qRT-PCR).Laboratory indicators of the two groups were compared and analyzed.Pearson method was used to analyze the correlation between serum HSP70,HSF1 mRNA levels and clinical indicators in patients with GDM;receiver operating characteristic curve(ROC)analysis was made of the predictive value of HSP70,HSF1,high-sensitivity C-reactive protein(hs-CRP)and cystatin C on adverse preg-nancy outcomes in GDM patients.Results Compared with the control group,the levels of fasting blood glucose,glycosylated hemoglobin(HbA1c)and creatinine,uric acid,hs-CRP,cystatin C,HSP70[(0.30±0.10)μg/L vs.(0.21±0.09)μg/L]and HSF1 mRNA(1.99±0.35 vs.1.03±0.32)in the GDM group were significantly increased(all P<0.05).There were 13(7.56%)cases of adverse pregnancy outcomes in the control group,and 91(53.22%)in the GDM group.The incidence of adverse pregnancy outcomes in the GDM group was much higher than that in the control group(P<0.05).Compared with the good pregnancy outcome group,the serum HSP70[(0.33±0.14)μg/L vs.(0.27±0.05)μg/L]and HSF1 mRNA(2.22±0.30 vs.1.73±0.41)in the poor pregnancy outcome group were significantly higher(all P<0.05).Serum HSP70 and HSF1 mRNA levels in patients with GDM were positively correlated(P<0.05),and serum HSP70 and HSF1 mRNA levels were positively correlated with fasting blood glucose,HbA1c,creatinine,uric acid,hs-CRP and cystatin C(all P<0.05).The results of ROC curve analysis showed that the areas under the cure(AUC)of HSP70,HSF1,hs-CRP,and cystatin C in predicting adverse pregnancy outcomes in GDM patients were 0.62,0.69,0.60,and 0.58,respectively.The AUC of serum HSP70 combined with HSF1 mRNA in predicting adverse pregnancy outcomes in GDM patients was 0.83,which was significantly higher than that predicted by serum HSP70,HSF1 mRNA,hs-CRP or cystatin C levels alone(all P<0.05).Conclusion Serum HSP70 and HSF1 are highly ex-pressed in GDM patients,and the combined detection of the two has a high predictive value for pregnancy outcome.