血清kallistatin、Netrin-4与早发型子痫前期患者外周血HMGB1-RAGE信号通路的关系及对妊娠结局的影响

Relationship between serum kallistatin,Netrin-4 and peripheral blood HMGB1-RAGE signaling pathway in patients with early-onset preeclampsia and their effect on pregnancy outcome

目的探讨血清人激肽释放酶抑制剂(kallistatin)、轴突导向因子4(Netrin-4)水平与早发型子痫前期(EOPE)患者外周血高迁移率族蛋白1(HMGB1)-晚期糖基化终末产物受体(RAGE)信号通路的关系及对妊娠结局的影响。方法选取2019年9月至2021年8月该院产科收治的EOPE患者(EOPE组,182例)及健康孕妇(对照组,91例)。比较两组血清kallistatin、Netrin-4、HMGB1、RAGE、核因子-κB p65(NF-κB p65)水平并进行相关性分析。根据EOPE患者的妊娠结局分为不良组(52例)和良好组(130例),并对不良妊娠结局的危险因素进行Logistic回归分析法。结果EOPE组患者血清kallistatin、Netrin-4水平低于对照组,HMGB1、RAGE、NF-κB p65水平高于对照组(P<0.05);血清HMGB1、RAGE、NF-κB p65水平与kallistatin、Netrin-4水平呈负相关(P<0.05)。EOPE组不良妊娠结局发生率为28.57%,单因素及多因素Logistic回归分析法结果显示,孕前高体质量指数(BMI)、24 h尿蛋白定量高水平、血肌酐高水平、D-二聚体高水平、血清kallistatin低水平、Netrin-4低水平均是EOPE患者发生不良妊娠结局的独立危险因素(P<0.05)。结论EOPE患者血清kallistatin、Netrin-4与HMGB1-RAGE信号通路蛋白表达呈负相关,孕前高BMI、24 h尿蛋白定量高水平、血肌酐高水平、D-二聚体高水平、血清kallistatin低水平、Netrin-4低水平是导致EOPE患者发生不良妊娠结局的独立危险因素。

Objective To investigate the relationship between the levels of serum human kallikrein inhibitor(kallistatin)and axon guidance factor 4(Netrin-4)and peripheral blood high mobility group box 1(HMGB1)-receptor for advanced glycation end products(RAGE)signaling pathway in patients with early-onset preeclampsia(EOPE)and their effect on pregnancy outcome.Methods Patients with EOPE(EOPE group,182 cases)and healthy pregnant women(control group,91 cases)who were admitted in the Department of Obstetrics in the hospital from September 2019 to August 2021 were selected.The levels of serum kallistatin,Netrin-4,HMGB1,RAGE and nuclear factor-κB p65(NF-κB p65)in the two groups were compared and correlation analysis was performed.According to the pregnancy outcome of patients with EOPE,they were divided into poor group(52 cases)and good group(130 cases),and Logistic regression analysis of risk factors for adverse pregnancy outcomes was performed.Results The levels of serum kallistatin and Netrin-4 in the EOPE group were lower than those in the control group,and the levels of serum HMGB1,RAGE and NF-κB p65 were higher than those in control group(P<0.05).The levels of serum HMGB1,RAGE and NF-κB p65 were negatively correlated with the levels of kallistatin and Netrin-4(P<0.05).The incidence of adverse pregnancy outcomes in the EOPE group was 28.57%.Univariate and multivariate Logistic regression analysis showed that high BMI in pre-pregnancy,high 24 hours urinary protein quantitative level,high serum creatinine level,high D-dimer level,low serum kallistatin level and low Netrin-4 level were independent risk factors for adverse pregnancy outcomes in patients with EOPE(P<0.05).Conclusion The levels of serum kallistatin and Netrin-4 in the patients with EOPE are negatively correlated with the protein expression of HMGB1-RAGE signaling pathway.High BMI in pre-pregnancy,high 24 hours urine protein level,high serum creatinine level,high D-dimer level,low serum kallistatin level and low Netrin-4 level are independent risk factors for adverse pregnancy outcomes in patients with EOPE.