脂氧素A4、肿瘤坏死因子α与子痫前期的关系研究

The Study on the Relationship between LXA4,TNFα and Preeclampsia

目的：探讨脂氧素A4（LXA4）、肿瘤坏死因子α（TNFα）及LXA4/TNFα比值与子痫前期（PE）发生发展的关系。方法：准备在天津医科大学第二医院产科分娩的健康孕妇200例,于妊娠10~12周、16~20周及32~36周采集孕妇血清检测LXA4、TNFα水平及LXA4/TNFα比值,跟踪产检及妊娠结局。选取最终有完整产检资料及妊娠结局患者195例,分为发生PE 23例（研究组）,未发生PE 172例（对照组）,进一步将两组中在我院行剖宫产分娩的患者分为PE组17例及PE对照组20例,剖宫产后取胎盘组织,采用实时荧光定量聚合酶链反应法检测各组胎盘中TNFαmRNA及LXA4受体（FPR2/ALX）mRNA的表达,ELISA方法测定孕妇剖宫产前及新生儿脐血LXA4、TNFα及LXA4/TNFα比值水平。对胎盘组织中TNFαmRNA及FPR2/ALX mRNA的表达与血清中TNFα及LXA4水平进行相关性分析。结果：研究组、对照组孕妇血清LXA4及TNFα水平均随着妊娠进展呈上升趋势（P〈0.05）,研究组妊娠中、晚期LXA4及TNFα水平明显高于对照组（P〈0.05）;研究组妊娠中、晚期LXA4/TNFα比值明显低于对照组,且随着孕周的增加比值明显下降（P〈0.05）。妊娠中期LXA4≥2.8 ng/ml、TNFα≥3.7 ng/ml,LXA4/TNFα≤0.7时预测PE的约登指数分别为0.76、0.72、0.81。PE组胎盘组织中TNFαmRNA、FPR2/ALXmRNA的表达及新生儿脐血TNFα水平明显升高;孕妇外周血TNFα、LXA4水平与胎盘TNFαmRNA、FPR2/ALXmRNA表达水平均呈正相关。结论：PE患者体内存在LXA4及其受体的相对缺乏,LXA4/TNFα比值降低可预测PE发生发展。推测适当激活胎盘中更多的LXA4受体或外源性补充LXA4可能是治疗PE的新途径。

Objective： The explore the relationship between LXA4,TNFα,LXA4 /TNFα ratio and the occurrence and development of preeclampsia. M ethods： Serum of 10- 12 gestation weeks,16- 20 gestation weeks,32- 36 gestation weeks of 200 normal pregnant women who wanted to be delivered in the Second Hospital of Tianjin Medical University were collected. Their perinatal outcomes were followed up. 195 pregnancies who had intact obstetric materials and perinatal outcomes were divided into study group（ PE afterwards,n = 23） and control group（ no PE afterwards,n =172）. 17 pregnancies who chose caesarean section（ CS） in the Second Hospital of Tianjin Medical University were in PE group; 20 nomortensive pregnancies were in PE control group. Umbilical cord blood and placenta samples were collected after cesarean section. Quantitative real-time polymerase chain reaction was applied to assay the TNFα mRNA and FPR2 / ALX mRNA levels. ELISA was applied to assay the LXA4,TNFα and LXA4 / TNFα ratio levels in maternal serum before CS and umbilical cord blood. The correlation between TNFα and TNFα mRNA,LXA4 and FPR2 / ALX mRNA were analyzed. Results： Serum levels of LXA4 and TNFα increased with development of pregnant in both study and control groups（ P〈0. 05）. Serum levels of LXA4 and TNFα increased,while LXA4 / TNFα ratio decreased significantly from the second to third trimester in study group（ P〈0. 05）. Youden＇s index of predicting preeclampsia at the second trimester was 0. 76,0. 72 and0. 81 respectively when LXA4≥2. 8 ng / ml,TNFα≥3. 7 ng / ml and LXA4 / TNFα≤0. 7. Compared with PE control group,PE group had significantly higher TNFα level in umbilical cord blood and higher expressions of TNFα mRNA,FPR2 / ALX mRNA in placenta. The levels of TNFα and LXA4 in the peripheral blood were positively correlated with the expression of TNFα mRNA and FPR2 / ALX mRNA in placenta. Conclusions： There are relative lack of LXA4 and its receptors in preeclampsia patients. The decrease of LXA4 / TNFα ratio can predict the occurrence and development of preeclampsia. We suppose that supplied with exogenous LXA4 or activated more LXA4 receptor to ensure adequate levels may be a novel method for the treatment of preeclampsia.