VEGF和p53与正常妊娠和子痫前期关系的研究
发布时间：2019-06-16 15:18
【摘要】：研究背景及目的 子痫前期(preeclampsia, PE)是妊娠期特有的一种疾病,以妊娠20周后突发高血压、蛋白尿和水肿为主要特征。全球发病率约为5%-8%,发展中国家的发病率更高,每年约有超过63000位孕产妇死于子痫前期,严重威胁着母儿健康,是导致孕产妇和围生儿死亡的主要原因之一。子痫前期的病因和发病机制至今尚未明确,血管内皮受损和胎盘浅着床学说是目前研究的两大热点。既往研究表明,血管内皮生长因子(vascular endothelial growth factor, VEGF)在维持正常的血管内皮功能方面发挥着重要的作用。p53蛋白是抑癌基因p53的表达产物,研究显示p53在异常妊娠的胎盘组织中表达上调；另有研究证实,野生型的p53可间接的抑制VEGF的表达,从而发挥抑制血管生成的作用,此结论在肿瘤的发生中已得到证实,对于p53与子痫前期关系的研究尚未见报道。本研究通过检测VEGF和p53在子痫前期患者和正常晚期妊娠孕妇胎盘组织中的表达变化,探讨VEGF和p53在子痫前期发生、发展中的作用,为进一步寻找子痫前期的发病机制提供线索。 方法 本研究选取在山东大学齐鲁医院产科行剖宫产的60例孕妇为研究对象。研究对象均为单胎初产妇,其中,35例子痫前期患者(15例轻度子痫前期和20例重度子痫前期)作为实验组,25例正常晚期妊娠孕妇为对照组。胎盘娩出后10min内于胎盘母体面近脐带处,选择无出血和钙化点的区域,取1.0cm×1.0cm×1.0cm大小的胎盘组织,分别处理标记,采用免疫组织化学SP法检测各组胎盘组织中VEGF和p53蛋白的水平并进行比较。 结果 1. VEGF在子痫前期组和正常组胎盘组织的细胞浆中均有表达,主要表达于胎盘合体滋养细胞、细胞滋养细胞以及血管内皮细胞。重度子痫前期组胎盘组织中VEGF的表达明显低于正常组和轻度子痫前期组[平均光密度IOD：0.0073206(0.0001920-0.0793925)vs.0.0751931(0.0169233-0.1598209),P=0.000；0.0073206(0.0001920-0.0793925)vs.0.0956797(0.0116911-0.1347583),P=0.000]；轻度子痫前期组胎盘组织中VEGF的表达与正常组相比无显著差异[0.0956797(0.0116911-0.1347583)vs.0.0751931(0.0169233-0.1598209),P=0.834]。各组VEGF的表达量与孕周无显著相关性(正常组：r=0.103,P=0.625；轻度子痫前期组：r=0.321,P=0.244；重度子痫前期组：r=0.077,P=0.747)。 2.p53在子痫前期组和正常组胎盘组织的细胞核中均有表达,主要表达于细胞滋养层细胞、合体滋养层细胞以及绒毛间质滋养层细胞。子痫前期组胎盘组织中p53的表达明显高于正常组[4(3-5)vs.3(2-5),P=0.027；7(6-7)vs.3(2-5),P=0.000]；重度子痫前期组胎盘组织中p53的表达明显高于轻度子痫前期组[7(6-7)vs.4(3-5),P=0.000]。各组p53的表达量与孕周无显著相关性(正常组：r=-0.099,P=0.639；轻度子痫前期组：r=0.433,P=0.107；重度子痫前期组：r=0.253,P=0.281)。 3.相关性分析结果表明,VEGF和p53在胎盘组织中的表达呈显著负相关(r=-0.428,P=0.001)。 结论 1.VEGF在重度子痫前期患者胎盘组织中的表达较正常晚期妊娠孕妇和轻度子痫前期患者均显著降低,提示VEGF可能参与子痫前期的发病过程,而且可能与子痫前期的严重程度有关。 2.p53均表达于子痫前期患者和正常晚期妊娠孕妇的胎盘组织中,p53在子痫前期患者胎盘组织中的表达较正常孕妇显著升高,并且随着病情加重,表达量增强,这说明p53可能参与子痫前期的发生与发展。 3. VEGF和p53在胎盘组织中的表达成负相关,印证了p53可通过各种途径间接抑制VEGF的表达,VEGF的低表达可进一步加重子痫前期的病情。
[Abstract]:Background and purpose of the study Preeclampsia (PE) is a disease specific to pregnancy, and it is the main disease of high blood pressure, proteinuria and edema after 20 weeks of pregnancy. The global incidence is about 5 per cent to 8 per cent, with a higher incidence of developing countries and more than 63,000 maternal deaths per year from pre-eclampsia, a serious threat to maternal health and a major cause of maternal and perinatal mortality I. The etiology and pathogenesis of pre-eclampsia have not yet been clear, and the vascular endothelial damage and the placental shallow-implantation theory are the two major heat of the present study. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an important role in maintaining normal vascular endothelial function The expression of p53 protein is an expression product of the tumor suppressor gene p53, and the expression of p53 in the placenta of the abnormal pregnancy is shown in the study. The results show that the wild-type p53 can indirectly inhibit the expression of VEGF, thereby exerting the effect of inhibiting angiogenesis, and the conclusion has been proved in the occurrence of the tumor. The study of the relationship between p53 and preeclampsia has not yet been reported. The effect of VEGF and p53 in the preeclampsia and the development of preeclampsia was discussed by detecting the changes of the expression of VEGF and p53 in the preeclampsia and in the normal and late-stage pregnant women. Soo. Methods 60 pregnant women with cesarean section in the obstetrical department of Qilu Hospital of Shandong University were selected In this study,35 cases of preeclampsia (15 mild preeclampsia and 20 severe preeclampsia) were used as experimental group and 25 normal and late pregnancy. The expression of VEGF and p53 protein in the placenta of each group was detected by immunohistochemical SP method. go hand in hand Results 1. The expression of VEGF in the cytoplasm of the preeclampsia group and the normal group of the placenta was mainly expressed in the trophoblast of the placenta, and the cells trophoblast. The expression of VEGF in the placental tissue of the severe preeclampsia group was significantly lower than in the normal group and the mild preeclampsia group[mean optical density IOD: 0.0073206 (0.0001920-0.0793925) vs. 0.0751931 (0.0169233-0.1598209), P = 0.000; 0.0073206 (0.0001920-0.0793925) vs. 0.0956797 (0.0116911-0.1347583), P = 0.000]; the expression of VEGF in the placental tissue of the preeclampsia group did not differ significantly from the normal group[0.0956797 (0.0116911-0.1347583) vs. 0.0751931 (0.0169233-0.1598209). P = 0.834]. The expression of VEGF in each group had no significant correlation with gestational weeks (normal group: r = 0.103, P = 0.625; pre-eclampsia group: r = 0.321, P = 0.244; severe preeclampsia group: r = 0.077 2. p53 was expressed in the nucleus of the preeclampsia group and the normal group of the placental tissues, mainly expressed in the cell trophoblast cell, the body trophoblast cell, The expression of p53 was significantly higher in the preeclampsia group than in the normal group[4 (3-5) vs.3 (2-5), P = 0.027;7 (6-7) vs.3 (2-5), P = 0.000]; the expression of p53 in the placental tissues of the preeclampsia group was significantly higher than that of the mild preeclampsia group[7 (6-7) vs.4 (3- 5), P = 0.000]. The expression of p53 in each group had no significant correlation with gestational weeks (normal group: r =-0.099, P = 0.639; pre-eclampsia group: r = 0.433, P = 0.107; severe preeclampsia group: r = 0.2 (53, P = 0.281).3. The correlation analysis showed that the expression of VEGF and p53 was negatively correlated with the expression of p53 in the placenta (r =-0). .4 Conclusion 1. The expression of VEGF in the placenta of the patients with severe preeclampsia is significantly lower than that of the normal and mild preeclampsia, suggesting that VEGF may be involved in the pathogenesis of preeclampsia. And may be related to the severity of preeclampsia. 3. The expression of VEGF and p53 in the placenta is negatively correlated with the expression of VEGF and p53 in the placenta, and the expression of VEGF can be indirectly inhibited by various means.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.244
本文编号：2500635
[Abstract]:Background and purpose of the study Preeclampsia (PE) is a disease specific to pregnancy, and it is the main disease of high blood pressure, proteinuria and edema after 20 weeks of pregnancy. The global incidence is about 5 per cent to 8 per cent, with a higher incidence of developing countries and more than 63,000 maternal deaths per year from pre-eclampsia, a serious threat to maternal health and a major cause of maternal and perinatal mortality I. The etiology and pathogenesis of pre-eclampsia have not yet been clear, and the vascular endothelial damage and the placental shallow-implantation theory are the two major heat of the present study. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an important role in maintaining normal vascular endothelial function The expression of p53 protein is an expression product of the tumor suppressor gene p53, and the expression of p53 in the placenta of the abnormal pregnancy is shown in the study. The results show that the wild-type p53 can indirectly inhibit the expression of VEGF, thereby exerting the effect of inhibiting angiogenesis, and the conclusion has been proved in the occurrence of the tumor. The study of the relationship between p53 and preeclampsia has not yet been reported. The effect of VEGF and p53 in the preeclampsia and the development of preeclampsia was discussed by detecting the changes of the expression of VEGF and p53 in the preeclampsia and in the normal and late-stage pregnant women. Soo. Methods 60 pregnant women with cesarean section in the obstetrical department of Qilu Hospital of Shandong University were selected In this study,35 cases of preeclampsia (15 mild preeclampsia and 20 severe preeclampsia) were used as experimental group and 25 normal and late pregnancy. The expression of VEGF and p53 protein in the placenta of each group was detected by immunohistochemical SP method. go hand in hand Results 1. The expression of VEGF in the cytoplasm of the preeclampsia group and the normal group of the placenta was mainly expressed in the trophoblast of the placenta, and the cells trophoblast. The expression of VEGF in the placental tissue of the severe preeclampsia group was significantly lower than in the normal group and the mild preeclampsia group[mean optical density IOD: 0.0073206 (0.0001920-0.0793925) vs. 0.0751931 (0.0169233-0.1598209), P = 0.000; 0.0073206 (0.0001920-0.0793925) vs. 0.0956797 (0.0116911-0.1347583), P = 0.000]; the expression of VEGF in the placental tissue of the preeclampsia group did not differ significantly from the normal group[0.0956797 (0.0116911-0.1347583) vs. 0.0751931 (0.0169233-0.1598209). P = 0.834]. The expression of VEGF in each group had no significant correlation with gestational weeks (normal group: r = 0.103, P = 0.625; pre-eclampsia group: r = 0.321, P = 0.244; severe preeclampsia group: r = 0.077 2. p53 was expressed in the nucleus of the preeclampsia group and the normal group of the placental tissues, mainly expressed in the cell trophoblast cell, the body trophoblast cell, The expression of p53 was significantly higher in the preeclampsia group than in the normal group[4 (3-5) vs.3 (2-5), P = 0.027;7 (6-7) vs.3 (2-5), P = 0.000]; the expression of p53 in the placental tissues of the preeclampsia group was significantly higher than that of the mild preeclampsia group[7 (6-7) vs.4 (3- 5), P = 0.000]. The expression of p53 in each group had no significant correlation with gestational weeks (normal group: r =-0.099, P = 0.639; pre-eclampsia group: r = 0.433, P = 0.107; severe preeclampsia group: r = 0.2 (53, P = 0.281).3. The correlation analysis showed that the expression of VEGF and p53 was negatively correlated with the expression of p53 in the placenta (r =-0). .4 Conclusion 1. The expression of VEGF in the placenta of the patients with severe preeclampsia is significantly lower than that of the normal and mild preeclampsia, suggesting that VEGF may be involved in the pathogenesis of preeclampsia. And may be related to the severity of preeclampsia. 3. The expression of VEGF and p53 in the placenta is negatively correlated with the expression of VEGF and p53 in the placenta, and the expression of VEGF can be indirectly inhibited by various means.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.244
【参考文献】
相关期刊论文 前1条
1 傅勤;林建华;;血管内皮生长因子在子痫前期发病机制中的研究[J];国外医学.妇产科学分册;2006年01期
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