【作者】 王慧玲；

【导师】 张新宇；

【作者基本信息】 大连医科大学 ， 妇产科学， 2007， 硕士

【摘要】 目的:子痫前期是一种妊娠特异性高血压疾病,在世界范围内是威胁围产期母儿安全的一个主要原因,它影响大约7%~10%的妊娠,在发展中国家,孕产妇死亡率的15%~20%由子痫前期所致。尽管大量研究集中在子痫前期,但是此疾病的病因学仍有待被阐明。因此,识别起源的危险因子、发现有高危因素的人群,将帮助从根本上攻克这个重要的公共健康问题,从而为子痫前期的预防及治疗提供依据。胎盘滋养细胞分泌的白细胞介素-6 (IL-6)和胎盘生长因子(PLGF)参与正常胎盘的形成和发育,国内外一些研究认为它们表达异常可能与子痫前期的发生有关。本实验旨在通过对照性的研究方法,对子痫前期患者进行羊水中IL-6和胎盘中PLGF的测定,并对二者之间的相关性进行研究,以探讨IL-6和PLGF在子痫前期发病中的作用。方法:用双抗体夹心酶联免疫吸附法测定60例剖宫产分娩的产妇羊水中IL-6的水平,包括研究组30例,其中轻度子痫前期组9例,重度子痫前期组21例;对照组30例,因其他原因剖宫产的孕妇。采用免疫组化法测定两组病例胎盘中PLGF的表达;并对胎盘中PLGF和羊水中的IL-6作Pearson相关性分析。结果:1、羊水中IL-6检测结果:子痫前期组羊水中IL-6的水平明显低于对照组,差异有显著性(P<0.01);轻度子痫前期组羊水中IL-6的水平与对照组相比无明显差异(P>0.05);重度子痫前期组羊水中IL-6的水平与对照组相比有极显著差异(P<0.001)。重度子痫前期组羊水中IL-6的水平与轻度子痫前期组相比有显著差异(P<0.05)。2、PLGF的免疫组化染色定位结果:子痫前期组PLGF主要在胎盘合体滋养细胞胞浆中表达,在血管内皮细胞、绒毛间质细胞和胎盘蜕膜细胞中有少量表达。对照组PLGF主要在胎盘的合体滋养细胞胞浆中表达,在绒毛内毛细血管内皮细胞中有中等程度的表达,在绒毛间质细胞和胎盘蜕膜细胞中也有少量表达。子痫前期组胎盘中PLGF的表达部位与对照组相比无差异,但表达较弱。3、胎盘合体滋养细胞PLGF的表达结果:30例子痫前期组胎盘合体滋养细胞PLGF的表达明显低于对照组(P<0.001);其中轻度子痫前期组和重度子痫前期组的胎盘合体滋养细胞PLGF的表达均明显低于对照组(P<0.001;P<0.001)。4、胎盘中PLGF和羊水中IL-6比较结果:总体子痫前期组PLGF和IL-6的水平呈高度正相关(r=0.792,P<0.001),其中重度子痫前期组PLGF和IL-6的水平呈高度正相关(r=0.874,P<0.001),而轻度子痫前期组PLGF和IL-6的水平不相关(r=0.313,P=0.412);对照组二者水平呈高度正相关(r=0.822,P<0.001)。结论1.羊水中IL-6的水平下降与子痫前期的发生及病情的严重程度有关。2. PLGF主要由滋养细胞分泌,在正常妊娠胎盘的形成和发育中起重要作用。3.胎盘中PLGF的表达减少与子痫前期的发生有关,且PLGF的表达量与子痫前期的病情程度有明显关系,病情越重,胎盘中PLGF的含量越低。4.羊水中IL-6对胎盘滋养细胞分泌PLGF有诱导作用,羊水中IL-6下降时能使胎盘滋养细胞分泌PLGF也下降,二者协同作用引起滋养细胞侵袭过浅和胎盘血管重铸障碍,使胎盘灌注减少,胎盘缺血缺氧,从而加速子痫前期的发生。更多还原

【Abstract】 Objective:Preeclampsia (PE) is a hypertensive disorder specific to pregnancy and is a major cause of perinatal maternal and neonatal death and morbidity worldwide, affecting nearly 7%-10% of all pregnancies . As much as 15% to 20% of maternal mortality in developed countries can be attributed to PE. Despite the large number of studies focusing on PE, the etiology of this disease remains to be elucidated. Identification of genetic risk factors and of the populations with high risk of disease, could aid substantially in the attacking of this important public health problem and provide clues for the prevention or treatment of PE. Interleuin-6 (IL-6) and placenta growth factors (PLGF) come from trophoblastic cells contribute to normal placental formation and development. Some investigations presume their abnormal expression participate in the development of PE. By case-control study to detect the expression of IL-6 of amniotic fluid and PLGF of placenta in patients with PE, and analyzing their correlation ,to make an inquiry into the role of amniotic fluid IL-6 and placenta PLGF in development of PE.Methods:60 caesarean delivered parturient (including study group 30 cases, among them 9 mild PE cases, 21 sever PE cases; control group 30 cases, they were performed section caesarean due to other reasons) were studied. Amniotic fluid levels of IL-6 was measured by enzyme linked immunosorbent assay (ELISA) and expression of PLGF in the placenta determined by immuno-histochemistry. To IL-6 and PLGF make Pearson correlation analysis.Results1. IL-6 of amniotic fluid measurement result: Amniotic fluid concentrations of IL-6 in PE group was significantly lower than that of control group(P<0.01);amniotic fluid concentrations of IL-6 in mild PE group had no significant differences with that of control group ( P > 0.05 ) ;amniotic fluid concentrations of IL-6 in server PE group was significantly lower Than that of control group(P<0.001); amniotic fluid concentrations of IL-6 in server PE group was significantly lower Than that of mild PE group(P<0.05).2. PLGF immuno-histochemistry dyeing location result: In PE group, PLGF expressed mainly in the cytoplasm of syncytiotrophoblastic cell, there was little PLGF expression in the endothelial cell of micrangium of villus, the mesenchymal cell of villus and decidual cell of placenta. In control group, PLGF expressed mainly in the cytoplasm of syncytiotrophoblastic cell, in the endothelial cell of micrangium of villus we detected average degree PLGF expression, we also observed little PLGF expression in the mesenchymal cell of villus and decidual cell of placenta. PLGF expression location In PE group had no differences with that of control group, but present weakly positive expression.3. PLGF expression result of syncytiotrophoblastic cell of placenta: The level of PLGF expression in syncytiotrophoblastic cell of placenta in 30 cases of PE group was significantly lower Than that of control group(P<0.001); among them the level of PLGF expression in syncytiotrophoblastic cell of placenta in both mild and server PE group was significantly lower Than that of control group(P<0.001; P<0.001).4. PLGF of placenta and IL-6 of amniotic fluid comparison result: Totality in PE group, levels of PLGF correlate with concentrations of IL-6(r=0.874,P<0.001),among them in server PE group, levels of PLGF correlate with concentrations of IL-6(r=0.874,P<0.001), but in mild PE group, levels of PLGF incorrelate with concentrations of IL-6(r=0.313,P=0.412); In control group, levels of PLGF correlate with concentrations of IL-6(r=0.822,P<0.001).Conclusions1、The decreased levels of IL-6 in the amniotic fluid is associated with the development of PE and correlates with the severity of preeclampsia.2、PLGF is secreted by trophocyte mainly, which plays an important role in the normal placental formation and development.3、The decreased expression of PLGF in the placenta is associated with the development of PE and expression of PLGF correlates with the severity of preeclampsia significantly, more serious PE, less PLGF expression of placenta.4、IL-6 of amniotic fluid can induce trophocyte of placenta to secret PLGF. The decreased levels of IL-6 of amniotic fluid can lead to decreased levels of PLGF. The decreased levels of IL-6 and PLGF might lead to shallow trophoblastic invasion followed by an incomplete remodelling of the maternal vascular structures, leads to uteroplacental insufficiency, ischemia and hypoxia, to accelerate development of PE.更多还原