瘦素在妊娠期高血压疾病母体血浆以及胎盘中的表达

The Expressions of Leptin in Maternal Plasma and Placenta of Hypertensive Disorder Complicating Pregnancy

目的探讨瘦素（leptin）在正常妊娠以及妊娠期高血压疾病母体血浆以及胎盘中的表达。方法采用前瞻性的研究方法，对孕早期血压正常的180例孕妇，保留妊娠10～14、20～24、30～34周以及终止妊娠后24h母体血浆、胎盘，根据随访结局分为子痫前期组（4例重度、6例轻度），妊娠期高血压组（12例）和正常妊娠组（22例，选自158例正常妊娠）。用ELISA法测定不同时间段母体血浆瘦素浓度，采用免疫组织化学法检测瘦素在胎盘组织中的定位和表达；采用QF-RT-PCR法检测胎盘中瘦素mRNA的表达水平。同时选取15例未孕健康妇女作为未孕对照组。结果正常妊娠孕妇母体血浆瘦素浓度随妊娠的进展逐渐升高；妊娠期子痫前期组的血浆瘦素浓度明显高于同期正常妊娠组，差异均有极显著性意义（P〈0．01），而妊娠期高血压组与正常妊娠组比较差异均无显著性意义（P〉0．05）；终止妊娠后24h所有病例母体血浆瘦素水平急剧下降，接近正常未孕水平。瘦素表达分布于胎盘绒毛合体滋养细胞、细胞滋养细胞；瘦素蛋白和mRNA表达强度在正常妊娠、妊娠期高血压、子痫前期依次上升，差异均有极显著性意义（P〈0．01）。结论子痫前期患者母体血浆瘦素水平在妊娠早期就已经明显升高，随着病情加重，胎盘分泌的瘦素逐步增加，是预示妊娠期高血压疾病病情严重程度的敏感信号分子之一。

Objective To investigate the expression of leptin in maternal plasma and placenta of hypertensive disorder complicating pregnancy （HDCP）. Methods A prospective study was performed on 180 pregnant women with previously normal blood pressure. Maternal blood plasma was collected at 10-14, 20-24, 30-34 gestational weeks and 24 h after delivery and placenta reserved. Based on pregnancy outcomes, the subjects were divided into preeclamptic group （severe for 4 cases and mild for 6 eases）, gestational hypertension group （12 cases） and healthy normal pregnant group （22 cases, selected from 158 normal healthy pregnant women by random）. Maternal blood plasma levels of leptin were determined by enzyme-llnked immunoassay technique, the expression and location of leptin in placenta were assayed by using immunohistochemistry （SP）, and the expression of leptin mRNA in placenta was detected by using quantitative fluorescent RT-PCR. At the same time, 15 healthy women without pregnancy were selected as non-pregnant group. Results The levels of maternal plasma leptin in normal healthy pregnant group were elevated with the development of pregnancy. The levels of leptin in preeclampsia were significantly higher than in healthy normal pregnant group at the same stages （P〈0.01）, but no change existed between gestational hypertension and normal pregnant group （P〉0. 05）. The levels of maternal plasma leptin were rapidly dropped into the levels of non-pregnancy on all subjects. The leptin in placenta was located in the cytoplasm of villous syneytiotrophoblast, cytotrophoblast and vascular endothelial cells. The expression intensity of leptin protein and mRNA in preeclampsia was greater than in gestational hypertension （P〈0.01）, and the intensity in gestational hypertension group was greater than in healthy normal pregnancy group by turn （P〈0. 01）. Conclusion The maternal plasma levels of leptin in preeclampsia are higher than in normal healthy pregnant women in the first trimester, and leptin protein secreted by placenta is elevated with the aggravated placental hypoxia. Leptin can be used as a sensitive signaling molecule of HDCP.