本文關(guān)鍵詞： 稽留流產(chǎn) 鄰苯二甲酸酯 凋亡 Bax Bcl-2　出處：《復(fù)旦大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：[目的]通過臨床資料統(tǒng)計(jì)與實(shí)驗(yàn)研究相結(jié)合的方法,揭示鄰苯二甲酸酯(PAEs)與稽留流產(chǎn)的關(guān)系,并初步探討其發(fā)病機(jī)制。[方法](1)通過病例-對(duì)照回顧性研究,收集1993年-2012年我院稽留流產(chǎn)病例,共計(jì)1945例,對(duì)比1874例妊娠20周內(nèi)的單胎活孕妊娠者的病例資料。通過卡方檢驗(yàn)和logistic回歸分析,分析與稽留流產(chǎn)發(fā)病相關(guān)的高危因素,探討環(huán)境等因素在稽留流產(chǎn)中可能的影響。(2)研究稽留流產(chǎn)病人中鄰苯二甲酸酯(PAEs)的暴露情況：留取原因不明的稽留流產(chǎn)病人及正常妊娠者各150份同期尿液標(biāo)本。采用超高效液相色譜-質(zhì)譜法分別檢測(cè)尿液中13種鄰苯二甲酸酯代謝產(chǎn)物水平,研究稽留流產(chǎn)病人的鄰苯二甲酸酯(PAEs)暴露情況。(3)體外試驗(yàn)：觀察人滋養(yǎng)層細(xì)胞系(HTR-8)在不同濃度DEHP (PAEs最常見的一種)作用下細(xì)胞活力、凋亡及細(xì)胞周期變化情況,初步探討其凋亡相關(guān)機(jī)制。[結(jié)果](1)本案logistic回歸多因素分析篩選出5個(gè)獨(dú)立危險(xiǎn)因素,將其按OR值由大至小進(jìn)行排列如下：乙型肝炎病毒攜帶者(OR 8.126,CI4.688-14.084),貧血(OR 5.498,CI 2.243-13.473),初產(chǎn)婦(OR 2.305,CI 2.013-2.638),自然流產(chǎn)史(OR 2.359,CI 1.703-3.268),室外職業(yè)者(OR1.777,CI 1.538-2.052)。研究近年來稽留流產(chǎn)獨(dú)立因素構(gòu)成變化顯示：室外職業(yè)及環(huán)境污染構(gòu)成比升高(P0.05)與稽留流產(chǎn)發(fā)病數(shù)增加有關(guān)；而流產(chǎn)≥3次、自然流產(chǎn)病史、貧血和乙肝病毒攜帶者的構(gòu)成比變化與稽留流產(chǎn)無明顯相關(guān)(P0.05)；同樣,初產(chǎn)婦這一稽留流產(chǎn)危險(xiǎn)因素,占比呈明顯下降與稽留流產(chǎn)發(fā)病數(shù)升高不符合。(2)超高效液相色譜-質(zhì)譜法檢測(cè)結(jié)果：DEHP的三種代謝產(chǎn)物(MEHP、MEHHP、MEOHP)及DMP代謝產(chǎn)物MMP在病例組尿液中檢出水平顯著高于對(duì)照組(P0.05)。而DEP的代謝產(chǎn)物MEP在病例組尿液中檢出水平卻顯著低于對(duì)照組(P0.05)。在相關(guān)性分析中,MEHP與雌激素中度相關(guān),而MMP與孕激素中度相關(guān)。(3)體外研究發(fā)現(xiàn)：①DEHP≤20ng/ml作用于HTR-8細(xì)胞48h未發(fā)現(xiàn)明顯毒性作用；DEHP 15ng/ml作用24小時(shí)能抑制HTR-8細(xì)胞的凋亡,同時(shí)明顯延長(zhǎng)細(xì)胞S期,減少GO/Gl期阻滯。DEHP 15ng/ml作用HTR-8細(xì)胞系6小時(shí),發(fā)現(xiàn)Bax表達(dá)降低而Bcl-2表達(dá)上升,可能是小劑量DEHP抑制細(xì)胞凋亡的機(jī)制。②DEHP≥30ng/ml作用HTR-8細(xì)胞24到48小時(shí),HTR-8細(xì)胞活性明顯受抑制(P0.05); 30ng/ml的DEHP能促進(jìn)HTR-8細(xì)胞凋亡,同時(shí)顯著性縮短細(xì)胞S期,增加GO/G1期阻滯。[結(jié)論](1)室外職業(yè)者、初產(chǎn)婦、自然流產(chǎn)病史、貧血和乙肝病毒攜帶者可能是稽留流產(chǎn)發(fā)生的獨(dú)立危險(xiǎn)因素,其中僅有室外職業(yè)者及未知因素的構(gòu)成比隨稽留流產(chǎn)發(fā)病數(shù)增加而升高。初步推論生育史、合并癥不能解釋稽留流產(chǎn)發(fā)病數(shù)的升高,而環(huán)境污染等不明原因可能是稽留流產(chǎn)病例數(shù)升高的重要原因之一。(2)稽留流產(chǎn)病人部分鄰苯二甲酸酯暴露情況明顯高于對(duì)照組,表明環(huán)境污染物-鄰苯二甲酸酯與近年來稽留流產(chǎn)高發(fā)病數(shù)有關(guān)。(3) DEHP 15ng/ml對(duì)人早孕滋養(yǎng)細(xì)胞毒性不明顯,并能抑制其凋亡,促進(jìn)生長(zhǎng)。其原因可能與小劑量的DEHP能下調(diào)Bax表達(dá),上調(diào)Bcl-2的表達(dá)有關(guān),是稽留流產(chǎn)發(fā)生的機(jī)制之一。
[Abstract]:[Objective] by the combination of statistical methods and experimental study of the clinical data, reveals the adjacent benzene two formic acid ester (PAEs) and the relationship between missed abortion, and to explore its pathogenesis. Methods: (1) through retrospective case-control study, collected in our hospital in 1993 -2012 missed abortion patients, a total of 1945 cases and compared with 1874 cases of singleton pregnancy within 20 weeks of pregnancy who live cases. Through chi square test and logistic regression analysis, analysis of risk factors associated with the incidence of missed abortion, to explore the impact of environmental factors may in missed abortion. (2) to study the adjacent benzene two formic acid ester with abortion patients (PAEs) exposure: take2ml of unexplained abortion patients and normal pregnant women during the same period. 150 copies of urine samples in the urine of 13 kinds of phthalate ester two formic acid metabolites were detected by ultra performance liquid chromatography mass spectrometry. The research of missed abortion patients Two people of phthalic acid ester (PAEs) exposure. (3) in vitro: Observation of human trophoblast cell line (HTR-8) in different concentrations of DEHP (one of the most common PAEs) cell viability under the effect of changes in cell cycle and apoptosis, to explore the mechanism of apoptosis related results (1)]. In the case of multiple logistic regression analysis identified 5 independent risk factors, according to the OR value from large to small order as follows: hepatitis B virus (OR 8.126, CI4.688-14.084), anemia (OR 5.498, CI 2.243-13.473), primipara (OR 2.305, CI 2.013-2.638), the history of spontaneous abortion (OR 2.359 CI, 1.703-3.268), outdoor occupation (OR1.777, CI 1.538-2.052). The independent risk factors of missed abortion in recent years showed that: the proportion of changes in environmental pollution and increase of outdoor occupation (P0.05) is associated with increased incidence of missed abortion and abortion; more than 3 times, abortion history, and anemia A hepatitis B virus carriers than changes and missed abortion and no obvious correlation (P0.05); similarly, the early maternal risk factors of missed abortion, the proportion decreased significantly with increased incidence of missed abortion is not met. (2) the detection results of ultra high performance liquid chromatography mass spectrometry: three metabolites DEHP (MEHP MEHHP, MEOHP, DMP) and metabolites of MMP detected in the case group in the urine was significantly higher than the control group (P0.05) and DEP. The metabolites of MEP in case group in the urine detection level was significantly lower than that of control group (P0.05). In correlation analysis, MEHP and estrogen and progesterone and MMP are moderate, moderate correlation. (3) in vitro was as follows: DEHP = 20ng/ml 48h in HTR-8 cells without obvious toxicity; 15ng/ml can inhibit the apoptosis of DEHP HTR-8 cells for 24 hours, at the same time prolong cell S phase, GO/Gl phase arrest of.DEHP 15ng/ml reduction Using HTR-8 cell lines for 6 hours showed that the expression of Bax decreased and Bcl-2 expression increased, is a possible mechanism of low dose of DEHP inhibits apoptosis. The DEHP 30ng/ml or HTR-8 cells 24 to 48 hours, the activity of HTR-8 cells was significantly inhibited (P0.05); 30ng/ml DEHP can promote the apoptosis of HTR-8 cells, and significantly reduce cell S phase, GO/G1 phase arrest increased. Conclusion: (1) outdoor occupation, primipara, spontaneous abortion history, anemia and hepatitis B virus carriers may be independent risk factors of missed abortion, which constitute the only outdoor occupation and unknown factors than with missed abortion incidence increased. We infer that reproductive history. Complications can not explain the increased incidence of missed abortion, and environmental pollution and other unknown reasons may be one of the important reasons of missed abortion were increased. The number of missed abortion patients (2) part of the adjacent benzene two phthalate exposure Significantly higher than the control group, indicating that the environmental pollutants - phthalate two formic acid ester and in recent years, the high incidence of missed abortion number. (3) DEHP 15ng/ml on trophoblast cell toxicity was not obvious, and can inhibit apoptosis and promote growth. The reason may be related to small doses of DEHP can downregulate Bax expression and up-regulated expression Bcl-2, is one of the mechanisms of missed abortion.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R714.21

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 楊柳;吳玉英;;稽留流產(chǎn)與沙眼衣原體和解脲支原體感染的關(guān)系及臨床意義[J];廣西醫(yī)學(xué);2007年12期

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本文編號(hào)：1555641