【作者】 侯磊；

【导师】 张曦； 崔世红；

【作者基本信息】 郑州大学 ， 妇产科学， 2003， 硕士

【摘要】 妊娠高血压综合征(pregnancy induced hypertension syndrome PIH)是产科常见的严重妊娠并发症之一，发病率高达9.4％，是导致孕产妇及围产儿死亡的重要原因，由于其病因不明确，至今仍是围产医学研究的重点。 妊高征胎盘生理性血管重铸障碍是妊高征胎盘的特征性病理改变，也是妊高征发病的中心环节。其产生的主要原因是滋养细胞功能异常，肝细胞生长因子(hepatocyte growth factor HGF)是新近发现的胎盘中对滋养细胞功能有重要的多效性调节作用的细胞因子，主要由绒毛间质细胞合成、分泌，受体c-met位于滋养细胞及绒毛血管内皮细胞表面，以旁分泌机制作用于滋养细胞和绒毛血管内皮细胞，通过刺激细胞的增殖、迁移、组织的形态发生促进生理性血管重铸形成、胎盘的发生、成熟、及绒毛血管网的建立。其在上述生理过程中所发挥的关键作用引起广泛关注。因此对妊高征胎盘HGF的相关研究将有助于探索其滋养细胞功能异常及继发病理改变的产生原因，从而阐明病因。 本课题采用免疫组织化学的方法，联合检测HGF和c-met在正常早、晚孕及妊高征胎盘中的表达情况，同时结合脐血流动力学指标及绒毛血管密度，研究其在正常孕期绒毛的表达规律、妊高征胎盘的表达变化及与妊高征病理改变间的相关关系。本研究目前国内尚未见报道。郑州大学2003届硕士研究生毕业论文妊高征胎盘HGF及受体c-met表达的研究 材料与方法1.研究对象分三组①正常早孕组，20例，为健康早孕妇女，均无内外科合并症。②正常晚孕组，20例，为健康晚孕妇女，均无产科并发症及内外科合并症。③妊高征组，共58例，按照第五版《妇产科学》诊断标准选取并分类，其中轻度妊高征17例，中度妊高征20例，重度妊高征21例，所有病例均无其它产科并发症及内外科合并症。2.第①组于人流术后即时取绒毛组织约109一409，第②、③组于胎盘娩出后30分钟内取胎盘母体面中央绒毛组织块约IcmX lemX lem;常规固定，石蜡包埋。采用免疫组化SP(Streptavidin/Peroxidas。)法，检测组织中HGF和c一met的表达;采用HE法做切片染色，计数绒毛血管密度;第②、③组研究对象均在产前一周内行彩色超声多普勒检测脐血流阻力指标。 结果1.临床一般资料轻、中、重度妊高征组与正常晚孕组比较，年龄、分娩孕周、基础血压均无显著差异(P>0 .05)，各妊高征组产前收缩压及与舒张压均较正常晚孕组显著升高，(P<0 .05)，重度妊高征组新生儿体重较正常晚孕组降低，差异有统计学意义(P<0 .05)。2.正常孕期胎盘HGF表达早孕组绒毛中，HGF表达于绒毛间质、细胞滋养细胞，合体滋养细胞及蜕膜细胞有少量表达。晚孕组胎盘中，HGF表达于绒毛间质细胞及绒毛血管内皮细胞，滋养细胞及蜕膜细胞均无表达。两组绒毛间质细胞HGF表达强度比较，晚孕组较早孕组表达强度降低，差异有统计学意义(P<0 .05)。3.妊高征组与正常晚孕组胎盘HGF表达比较表达定位无差异，绒毛间质细胞HGF表达强度比较:轻度及中度妊高征组与正常晚孕组比较，差异无统计学意义(P>0 .05，P>0 .05)、重度妊高征组较正常晚孕组显著降低，差异有统计学意义(P<0 .05)。HGF表达强度与妊高征病情呈负相关(r:二一0.319P<0.05)。4.正常孕期胎盘c一met表达早孕绒毛中，c一met表达于细胞滋养细胞、合体滋养细胞和蜕膜细胞，绒毛血管内皮细胞也有少量着色。绒毛间质无表达。晚孕胎盘c一met表达部位同早孕，两组绒毛滋养细胞c一met表达强度比较，晚孕组较早孕组降低，差异有统计学意义(P<0.05)。5.妊高征组与正常晚孕组胎盘c一et表达比较表达定位无差异，绒毛滋养细胞c一met表达强度比较:轻度及中度妊高征组与正常晚孕组比较，差异无统计学意义(P>0 .05，P>0.05);重度妊高征患者组较正常晚孕组显著升高，差异有统计学意义(P<0 .05)。c一met表达强度与妊高征病情呈正相关(rs=0 .286P<0 .05)。6.绒毛间质细胞HG郑州大学2003届硕士研究生毕业论文妊高征胎盘HGF及受体c-met表达的研究F表达与滋养细胞c一Inet表达相关性分析两者呈负相关(rs二一0.255P<0 .05)。7.HGF与脐血流阻力指标重度妊高征组的胎儿心脏收缩期末最大血流速度与舒张期末最大血流速度之比(S/D)、血管阻力指数(Rl)、血流搏动指数(Pl)三项脐血流阻力指标均高与对照组，差异有统计学意义(P<0 .05)。轻、中度妊高征各项脐血流阻力指标与对照组相比，差异无统计学意义(P>0 .05)。绒毛间质细胞HGF表达强度与S/D、Pl值呈负相关(rs二一0.376P(0.05，rs=一0.333P(0.05)。8.HGF与绒毛血管密度胎盘组织病理学检查显示:各妊高征组绒毛血管密度均较正常晚孕组明显降低，重度妊高征组与正常晚孕组相比，差异有统计学意义(P<0.05)。绒毛间质细胞HGF表达强度与绒毛血管密度呈正相关(rs=0 .246P<0 .05)。 结论1.早孕及晚孕绒毛中，HGF表达于绒毛的间质细胞及滋养细胞、血管内皮细胞，晚孕绒毛间质HGF表达强度低于早孕。表明HGF的分泌随孕周进展而下降，绒毛血管内皮细胞及滋养细胞的表达提示这些细胞可能存在HGF自分泌机制;2.妊高征胎盘更多还原

【Abstract】 Preganancy-Induced-Hypertension syndrome(PIH) is a common serious pregnant complication in obstetric department. The incidency rate of it is 9. 4%, it is an important cause of perinatal and maternal mortality. Because its etiology is undefined, it still be one of the most important subjects in Perinatology by now.Abnormal remodeling vasculature is the characteristic pathology in the placenta of PIH, it is also the crucial process of etiology of PIH and result from abnormal function of trophoblast (TB). Hepatocyte growth facor (HGF) is a kind of new cytokine that can regulate various function of TB. It is mainly producted by villous mesenchymal cell,its receptor occurs on the TB and vessel endothelial cells, HGF improved the establishment of remodeling vasculature, placentation and maturity of vessel web by stimulating the proliferation, invasion of cells and morphogen. So, theresearch for HGF is helpful to trace the reason of shallow invasion and clarify the etiology of PIH. The expression of HGF and c-met was measured by Immunohistochemistry here, and contacted with the villous vessel density and umbilicus hemodynamics, in order to elucidate the role of HGF on the etiology of PIH, and then provide theoretical foundation of prevention and treatment.Materials ands Methods 1. All subject were derived into three group: ﹖he early pregnant group (n=20), woman with normal early pregnancy;?the normal late pregnant group (n=20) ; (3) the PIH group (n=58), according to the diagnostic standard (OBSTETRICS AND GYNECOLOGY, the fifth edit), it is further subdivided into mi Id (n=17), middle (n=20) and severe group (n= 21). All patients were of without other complications of pregnancy and primary hypertension, renal disorders. 2. The biopsies were immediately collected after abortion or delivery, tissue was fixed in 10% formalin and embedded in paraffin wax for subsequent examination. 3. The expression of HGF and c-met were determined using immunohistochemistry and the villous vessel density were determined by the mean count of villous vessels under per high vertex after stained by HE, The parameters of umbilicus hemodynamics were obtained within one week before delivery by ultrasonography.Results 1. There are no significant difference between PIH group and the normal late pregnant group in mean ages , gestational weeks and the basic blood pressure (P>0. 05). The mean systolic and diastolic blood pressure of three group of PIH group were significantly higher than normal late pregnant group (P<0. 05) . The mean weight of newborns in sever PIH group was significantly lower than that of normal late pregnant group (P<0. 05). 2. The stong immunostaining of HGF was observes in villous mesenchymal cells, cytotrophoblasts in the placentas of normal early pregnancy. It also occured in the villous mesenchymal cells and vascular endometricalcells in the placentas of normal late pregnany. The intensity of HGF immunosytaining of mesenchymal cells in the placentas of late pregnant group was lower than that of normal early pregnancy group ( P<0. 05) . 3. The intensity of HGF of villous mesenchymal cells in sever PIH group was significantly lower than that of the normal late pregnant group (P<0. 05) .While it has no qualitative differences between the mild and middle PIH with the normal group ( P>0. 05). There was negative correlation between the intensity of HGF of villous mesenchymal cells and the state of PIH (rs=-0.319 P<0.05) . 4. The stong immunostaining of c-met was observes in trophoblasts in the placentas of normal early pregnancy. It also occured in the trophoblasts and vascular endometrical cells in the placentas of normal late pregnany, no staining was observed in villous mesenchymal cells. The intensity of c-met immunosytaining of trophoblasts in the placentas of normal late pregnant group was lower than that of normal early pregnant group. 5. The intensity of c-met in sever PIH group was significantly higher than that of the normal late pregnant group( P<0. 05), While it has no qualitative differences更多还原