VEGF和p53與正常妊娠和子癇前期關(guān)系的研究
發(fā)布時(shí)間：2019-06-16 15:18
【摘要】：研究背景及目的 子癇前期(preeclampsia, PE)是妊娠期特有的一種疾病,以妊娠20周后突發(fā)高血壓、蛋白尿和水腫為主要特征。全球發(fā)病率約為5%-8%,發(fā)展中國(guó)家的發(fā)病率更高,每年約有超過(guò)63000位孕產(chǎn)婦死于子癇前期,嚴(yán)重威脅著母兒健康,是導(dǎo)致孕產(chǎn)婦和圍生兒死亡的主要原因之一。子癇前期的病因和發(fā)病機(jī)制至今尚未明確,血管內(nèi)皮受損和胎盤(pán)淺著床學(xué)說(shuō)是目前研究的兩大熱點(diǎn)。既往研究表明,血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor, VEGF)在維持正常的血管內(nèi)皮功能方面發(fā)揮著重要的作用。p53蛋白是抑癌基因p53的表達(dá)產(chǎn)物,研究顯示p53在異常妊娠的胎盤(pán)組織中表達(dá)上調(diào)；另有研究證實(shí),野生型的p53可間接的抑制VEGF的表達(dá),從而發(fā)揮抑制血管生成的作用,此結(jié)論在腫瘤的發(fā)生中已得到證實(shí),對(duì)于p53與子癇前期關(guān)系的研究尚未見(jiàn)報(bào)道。本研究通過(guò)檢測(cè)VEGF和p53在子癇前期患者和正常晚期妊娠孕婦胎盤(pán)組織中的表達(dá)變化,探討VEGF和p53在子癇前期發(fā)生、發(fā)展中的作用,為進(jìn)一步尋找子癇前期的發(fā)病機(jī)制提供線索。 方法 本研究選取在山東大學(xué)齊魯醫(yī)院產(chǎn)科行剖宮產(chǎn)的60例孕婦為研究對(duì)象。研究對(duì)象均為單胎初產(chǎn)婦,其中,35例子癇前期患者(15例輕度子癇前期和20例重度子癇前期)作為實(shí)驗(yàn)組,25例正常晚期妊娠孕婦為對(duì)照組。胎盤(pán)娩出后10min內(nèi)于胎盤(pán)母體面近臍帶處,選擇無(wú)出血和鈣化點(diǎn)的區(qū)域,取1.0cm×1.0cm×1.0cm大小的胎盤(pán)組織,分別處理標(biāo)記,采用免疫組織化學(xué)SP法檢測(cè)各組胎盤(pán)組織中VEGF和p53蛋白的水平并進(jìn)行比較。 結(jié)果 1. VEGF在子癇前期組和正常組胎盤(pán)組織的細(xì)胞漿中均有表達(dá),主要表達(dá)于胎盤(pán)合體滋養(yǎng)細(xì)胞、細(xì)胞滋養(yǎng)細(xì)胞以及血管內(nèi)皮細(xì)胞。重度子癇前期組胎盤(pán)組織中VEGF的表達(dá)明顯低于正常組和輕度子癇前期組[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]；輕度子癇前期組胎盤(pán)組織中VEGF的表達(dá)與正常組相比無(wú)顯著差異[0.0956797(0.0116911-0.1347583)vs.0.0751931(0.0169233-0.1598209),P=0.834]。各組VEGF的表達(dá)量與孕周無(wú)顯著相關(guān)性(正常組：r=0.103,P=0.625；輕度子癇前期組：r=0.321,P=0.244；重度子癇前期組：r=0.077,P=0.747)。 2.p53在子癇前期組和正常組胎盤(pán)組織的細(xì)胞核中均有表達(dá),主要表達(dá)于細(xì)胞滋養(yǎng)層細(xì)胞、合體滋養(yǎng)層細(xì)胞以及絨毛間質(zhì)滋養(yǎng)層細(xì)胞。子癇前期組胎盤(pán)組織中p53的表達(dá)明顯高于正常組[4(3-5)vs.3(2-5),P=0.027；7(6-7)vs.3(2-5),P=0.000]；重度子癇前期組胎盤(pán)組織中p53的表達(dá)明顯高于輕度子癇前期組[7(6-7)vs.4(3-5),P=0.000]。各組p53的表達(dá)量與孕周無(wú)顯著相關(guān)性(正常組：r=-0.099,P=0.639；輕度子癇前期組：r=0.433,P=0.107；重度子癇前期組：r=0.253,P=0.281)。 3.相關(guān)性分析結(jié)果表明,VEGF和p53在胎盤(pán)組織中的表達(dá)呈顯著負(fù)相關(guān)(r=-0.428,P=0.001)。 結(jié)論 1.VEGF在重度子癇前期患者胎盤(pán)組織中的表達(dá)較正常晚期妊娠孕婦和輕度子癇前期患者均顯著降低,提示VEGF可能參與子癇前期的發(fā)病過(guò)程,而且可能與子癇前期的嚴(yán)重程度有關(guān)。 2.p53均表達(dá)于子癇前期患者和正常晚期妊娠孕婦的胎盤(pán)組織中,p53在子癇前期患者胎盤(pán)組織中的表達(dá)較正常孕婦顯著升高,并且隨著病情加重,表達(dá)量增強(qiáng),這說(shuō)明p53可能參與子癇前期的發(fā)生與發(fā)展。 3. VEGF和p53在胎盤(pán)組織中的表達(dá)成負(fù)相關(guān),印證了p53可通過(guò)各種途徑間接抑制VEGF的表達(dá),VEGF的低表達(dá)可進(jìn)一步加重子癇前期的病情。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R714.244
本文編號(hào)：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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R714.244
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 傅勤;林建華;;血管內(nèi)皮生長(zhǎng)因子在子癇前期發(fā)病機(jī)制中的研究[J];國(guó)外醫(yī)學(xué).婦產(chǎn)科學(xué)分冊(cè);2006年01期
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