【摘要】：目的:子宮內(nèi)膜異位癥是育齡期婦女中常見的慢性疾病,其發(fā)病機(jī)制尚不明確。子宮內(nèi)膜異位癥的臨床表現(xiàn)主要為繼發(fā)性痛經(jīng)、慢性盆腔痛、不孕等,嚴(yán)重影響著人們的生活。子宮內(nèi)膜異位癥本身雖是一種良性疾病,卻具有惡性腫瘤粘附、局部浸潤和遠(yuǎn)處轉(zhuǎn)移的特點。MMPs作為腫瘤轉(zhuǎn)移相關(guān)基因,參與多種腫瘤的發(fā)病過程,我們推測MMPs也參與了子宮內(nèi)膜異位癥的發(fā)生發(fā)展過程�，F(xiàn)已有大量研究提示nm23-H1可通過RAS途徑抑制MMPs的表達(dá),抑制細(xì)胞的轉(zhuǎn)移能力,從而參與多種腫瘤的發(fā)生、發(fā)展過程。前期實驗已證實nm23-H1在子宮內(nèi)膜異位癥的異位內(nèi)膜組織中的表達(dá)明顯低于正常子宮內(nèi)膜組,推測nm23-H1在子宮內(nèi)膜異位癥的發(fā)病過程中起到一定作用,然而在子宮內(nèi)膜異位癥中nm23-H1是否可通過影響MMPs的表達(dá)變化來影響子宮內(nèi)膜組織的侵襲、轉(zhuǎn)移能力尚未得到證實。本實驗旨在通過分析MMP-2、MMP-9在正常子宮內(nèi)膜組織及異位子宮內(nèi)膜組織中的表達(dá)變化,探討MMP-2、MMP-9在子宮內(nèi)膜異位癥發(fā)生、發(fā)展中的可能起到的作用,并結(jié)合前期試驗結(jié)果分析nm23-H1與MMP-2、MMP-9在子宮內(nèi)膜異位癥發(fā)生、發(fā)展中是否存在相關(guān)性,探討nm3-H1是否可通過RAS信號通路影響子宮內(nèi)膜異位癥的發(fā)展。方法:將收集到的正常子宮內(nèi)膜組織38例及異位子宮內(nèi)膜組織45例均分為兩份,其中1份用Trizol一步法提取組織總RNA,并將其逆轉(zhuǎn)錄成cDNA,采用實時熒光定量PCR技術(shù)定量檢測其中的MMP-2、MMP-9基因在正常和異位子宮內(nèi)膜組織中m RNA的表達(dá)情況;另一份提取組織總蛋白,采用Western Blot方法,檢測MMP-2、MMP-9基因在正常和異常子宮內(nèi)膜組織中蛋白的表達(dá)情況。結(jié)果:1、qRT-PCR實驗結(jié)果:(1)子宮內(nèi)膜異位癥組織中MMP-2基因的mRNA表達(dá)量為4.01±2.89,在正常子宮內(nèi)膜組MMP-2基因mRNA的表達(dá)量為1.40±1.13,將兩組中MMP-2基因mRNA的表達(dá)比較可發(fā)現(xiàn),異位內(nèi)膜組織中的表達(dá)明顯高于正常子宮內(nèi)膜組,,差異有統(tǒng)計學(xué)意義(t=-3.66,P=0.000,P0.05)。(2)子宮內(nèi)膜異位癥組織中MMP-9基因的mRNA表達(dá)量為3.04±2.77,正常子宮內(nèi)膜組MMP-9基因mRNA的表達(dá)量為0.99±0.86,將兩組中MMP-9基因mRNA的表達(dá)比較可發(fā)現(xiàn),異位內(nèi)膜組織中的表達(dá)明顯高于正常子宮內(nèi)膜組,差異有統(tǒng)計學(xué)意義(t=-3.158,P=0.000,P0.05)。(3)結(jié)合前期試驗,對nm23-H1與MMP-2、nm23-H1與MMP-9相關(guān)性的分析,發(fā)現(xiàn)前者r 1=-0.21,P0.05;后者r 2=-0.12,P0.05,提示在子宮內(nèi)膜異位癥中nm23-H1與MMP2、MMP-9存在負(fù)性相關(guān),但兩兩之間相關(guān)性不強。2、Western Blot實驗結(jié)果:經(jīng)研究發(fā)現(xiàn)MMP-2在子宮內(nèi)膜異位癥的異位內(nèi)膜組織中的蛋白表達(dá)為水平為1.64±0.62,正常子宮內(nèi)膜組MMP-2的蛋白表達(dá)量為0.61±0.31,兩者比較可見,MMP-2在異位子宮內(nèi)膜組織中的表達(dá)明顯高于正常子宮內(nèi)膜組,兩者間的差異有統(tǒng)計學(xué)意義(t=-0.75,P=0.027,P0.05)。結(jié)論:MMP-2、MMP-9基因在異位子宮內(nèi)膜組織中表達(dá)上調(diào),提示MMP-2、MMP-9在子宮內(nèi)膜異位癥的發(fā)生、發(fā)展中起到一定的作用。結(jié)合前期實驗分析發(fā)現(xiàn)在子宮內(nèi)膜異位癥中nm23-H1基因與MMP-2、MMP-9基因表達(dá)呈負(fù)相關(guān),但他們之間的相關(guān)性不強,故而若為驗證nm23-H1基因是否通過RAS途徑抑制MMP-2、MMP-9在異位內(nèi)膜組織中的表達(dá)需進(jìn)行進(jìn)一步研究。有關(guān)nm23-H1與MMP-2、MMP-9基因的在子宮內(nèi)膜異位癥的相關(guān)性研究,有助于促進(jìn)對內(nèi)異癥的進(jìn)一步認(rèn)識,為子宮內(nèi)膜異位癥的診斷、治療及預(yù)后提供新的標(biāo)靶。
[Abstract]:Objective: Endometriosis is a common chronic disease in women of childbearing age, and its pathogenesis is not clear. The clinical manifestations of endometriosis are secondary dysmenorrhea, chronic pelvic pain, and infertility. Endometriosis itself is a benign disease, but has the characteristics of malignant tumor adhesion, local infiltration and distant metastasis. MMPs, as a tumor metastasis-related gene, are involved in the pathogenesis of multiple tumors, and we assume that MMPs also participate in the development of endometriosis. It has been shown that nm23-H1 can inhibit the expression of MMPs by RAS, and inhibit the transfer ability of cells, thus participating in the occurrence and development of multiple tumors. The expression of nm23-H1 in the ectopic endometrial tissue of endometriosis is significantly lower than that of the normal endometrium, and it is presumed that the nm23-H1 plays a role in the pathogenesis of endometriosis. However, whether nm23-H1 in endometriosis can influence the invasion and metastasis of the endometrial tissue by influencing the expression change of MMPs has not been confirmed. The purpose of this study was to study the expression of MMP-2 and MMP-9 in the normal endometrium and the tissue of the ectopic endometrium, and to explore the possible role of MMP-2 and MMP-9 in the occurrence and development of endometriosis, and to analyze the expression of nm23-H1 and MMP-2 in the early-stage test. MMP-9 is related to the occurrence and development of endometriosis, and whether nm3-H1 can influence the development of endometriosis through the RAS signal pathway. Methods: A total of 38 cases of normal endometrium and 45 cases of ectopic endometrium were divided into two groups. One of them was used to extract total RNA from the tissue by Trizol one-step method and reverse transcription into cDNA. The expression of MMP-2 was detected by real-time fluorescence quantitative PCR. The expression of MMP-9 gene in normal and ectopic endometrium was detected by Western Blot method, and the expression of MMP-2 and MMP-9 in normal and abnormal endometrial tissues was detected. Results: (1) The mRNA expression of MMP-2 gene in the tissue of endometriosis was 4.01-2.89, and the expression of MMP-2 mRNA in the normal endometrium was 1. 40-1.13, and the expression of MMP-2 mRNA in the two groups could be found. The expression of ectopic endometrium was significantly higher than that of normal endometrium (t =-3.66, P = 0.000, P0.05). (2) The expression of MMP-9 in the tissue of endometriosis was 3.04-2.77, and the expression of MMP-9 mRNA in the normal endometrium was 0.99-0.86. The expression of MMP-9 mRNA in the two groups was found to be higher than that of the normal endometrium. The difference was significant (t =-3.158, P = 0.000, P0.05). (3) The correlation between nm23-H1 and MMP-2, nm23-H1 and MMP-9 was analyzed in the early stage. The results showed that there was negative correlation between nm23-H1 and MMP2 and MMP-9 in endometriosis. The results showed that the expression of MMP-2 in the ectopic endometrium of endometriosis was 1.64-0.62, and the expression of MMP-2 in the normal endometrium was 0.61-0.31. The expression of MMP-2 in the tissue of the ectopic endometrium was significantly higher than that of the normal endometrium. The difference between the two groups was statistically significant (t =-0.75, P = 0.027, P0.05). Conclusion: The expression of MMP-2 and MMP-9 in ectopic endometrium is up-regulated, suggesting that MMP-2 and MMP-9 play a role in the pathogenesis and development of endometriosis. The expression of nm23-H1 gene in endometriosis was negatively correlated with the expression of MMP-2 and MMP-9, but the correlation between them was not strong, and the expression of MMP-2 and MMP-9 in the tissue of ectopic endometrium was further studied. The study of the correlation between nm23-H1 and MMP-2 and MMP-9 in endometriosis can help to promote the further understanding of endometriosis and provide a new target for the diagnosis, treatment and prognosis of endometriosis.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R711.71

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 趙晨光;;腹壁切口子宮內(nèi)膜異位癥12例臨床分析[J];基層醫(yī)學(xué)論壇;2016年36期

2 呂春紅;王連珠;;保守性手術(shù)聯(lián)合米非司酮與孕三烯酮治療子宮內(nèi)膜異位癥療效觀察[J];實用臨床醫(yī)藥雜志;2016年23期

3 楊琴;吳海波;張艷琴;王寧;王文娟;;基質(zhì)金屬蛋白酶-2在子宮內(nèi)膜異位癥中的表達(dá)及應(yīng)用價值[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2016年32期

4 沈燁;曹雪梅;;子宮內(nèi)膜異位癥術(shù)后藥物治療現(xiàn)狀及進(jìn)展[J];現(xiàn)代醫(yī)藥衛(wèi)生;2016年21期

5 易金玲;朱君;劉雁林;沈艷麗;;腹腔鏡術(shù)后應(yīng)用促性腺激素釋放激素激動劑治療子宮內(nèi)膜異位癥的臨床效果[J];中國婦幼保健;2016年19期

6 陳帆;楊華娣;;腹腔鏡手術(shù)聯(lián)合促性腺激素釋放激素激動劑對子宮內(nèi)膜異位癥不孕的臨床療效研究[J];中國內(nèi)鏡雜志;2016年09期

7 魏馨;劉鵬敏;黃黎;;子宮內(nèi)膜異位癥患者在位內(nèi)膜的MMP-9和VEGF的表達(dá)[J];臨床醫(yī)學(xué)工程;2016年09期

8 莫倩珍;沈家欣;劉靜;;中國肺癌患者M(jìn)MP-2表達(dá)臨床生物學(xué)意義的Meta分析[J];臨床醫(yī)學(xué)研究與實踐;2016年13期

9 李華;陳麗;陳丹;黃欣欣;姜雋楹;陳莎莉;吳偉芳;;卵巢子宮內(nèi)膜異位囊腫復(fù)發(fā)65例病例分析[J];中國婦幼保健;2016年14期

10 張巖;楊飚;徐文萍;張安樂;蔣莉莉;;促性腺激素釋放激素激動劑聯(lián)合左炔諾孕酮宮內(nèi)節(jié)育系統(tǒng)用于子宮內(nèi)膜異位癥術(shù)后效果[J];中國臨床保健雜志;2016年04期

，

本文編號：2345511