本文關(guān)鍵詞：子宮肌瘤患者血清MMP-9、EGF水平及相關(guān)性研究　出處：《承德醫(yī)學(xué)院》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 子宮肌瘤 MMP-9 EGF 血清學(xué) 相關(guān)性

【摘要】：子宮肌瘤(uterine myoma,UM)即子宮平滑肌瘤(uterine leiomyoma,UL),又被稱為子宮纖維瘤(uterine fibroid,UF),是臨床婦科最常見的女性生殖器良性腫瘤。據(jù)統(tǒng)計(jì),30歲以上的育齡期女性約有超過20%的人群患有子宮肌瘤,我國(guó)女性子宮肌瘤的患病高峰在41-50歲之間,此年齡段的患病率約為54.9%。因?yàn)榇蠖鄶?shù)的子宮肌瘤很少甚至根本沒有癥狀,所以臨床調(diào)查所報(bào)道的發(fā)病率可能遠(yuǎn)遠(yuǎn)低于其真正的發(fā)病率。且隨著社會(huì)的發(fā)展及生活環(huán)境的變遷,子宮肌瘤的發(fā)病率正在逐漸升高,且發(fā)病年齡更趨于年輕化。現(xiàn)階段,子宮肌瘤的發(fā)病機(jī)制仍尚未完全明了,其發(fā)病機(jī)理及病因是多因素、多環(huán)節(jié)的。多項(xiàng)研究表明,除雌、孕激素外,子宮肌瘤的發(fā)生、發(fā)展還與基質(zhì)金屬蛋白酶家族(MMPs)及多種生長(zhǎng)因子有密切關(guān)系。有相關(guān)文獻(xiàn)報(bào)道,子宮肌瘤形成可能與細(xì)胞外基質(zhì)(ECM)的形成和蓄積有一定關(guān)系,而MMPs正是降解細(xì)胞外基質(zhì)的重要家族,其中MMP-9則是MMPs家族中發(fā)揮降解與重構(gòu)作用的重要成員。MMP-9是明膠酶中的一種,它的底物是構(gòu)成基底膜和細(xì)胞外基質(zhì)的重要成分--Ⅳ型膠原。近年研究表明,MMP-9與多種婦科良、惡性疾病密切相關(guān)。周秀萍等通過研究發(fā)現(xiàn)子宮肌瘤細(xì)胞中MMP-9水平顯著增加,可能與子宮肌瘤的發(fā)生有一定關(guān)系。據(jù)文獻(xiàn)報(bào)導(dǎo),雌激素對(duì)子宮肌瘤的作用是間接的,它是以生長(zhǎng)因子為中介因子而從中發(fā)揮作用的。主要的生長(zhǎng)因子包括表皮生長(zhǎng)因子(EGF)、轉(zhuǎn)移生長(zhǎng)因子-β(TGF-β)、胰島素樣生長(zhǎng)因子(IGF)、堿性成纖維生長(zhǎng)因子(b FGF)和血小板源性生長(zhǎng)因子(PDGF)等。研究發(fā)現(xiàn),雌激素可通過刺激雌激素反應(yīng)細(xì)胞產(chǎn)生EGF,EGF與EGFR表達(dá)水平上調(diào),從而參與子宮肌瘤的發(fā)病機(jī)制。本研究通過對(duì)子宮肌瘤患者血清中基質(zhì)金屬蛋白酶9(MMP-9)和表皮生長(zhǎng)因子(EGF)水平的測(cè)定,探討MMP-9和EGF的表達(dá)水平與子宮肌瘤的相關(guān)性。目的:本實(shí)驗(yàn)通過采集子宮肌瘤患者(病例組)及健康體檢者血清(對(duì)照組),測(cè)定兩組血清中基質(zhì)金屬蛋白酶-9(MMP-9)、表皮生長(zhǎng)因子(EGF)的表達(dá)水平,將兩種因子在病例組及對(duì)照組中的血清均值進(jìn)行比較;根據(jù)不同臨床病歷資料,將不同類型的子宮肌瘤患者的血清水平進(jìn)行組內(nèi)比較,進(jìn)而探討這兩種因子的血清表達(dá)水平與子宮肌瘤發(fā)生的相關(guān)性,及其是否可以作為子宮肌瘤的臨床檢測(cè)指標(biāo)。方法:選取2013.01~2014.01在承德市中心醫(yī)院行手術(shù)治療,術(shù)后病理回報(bào)為子宮肌瘤,且無其他合并癥的患者62例作為病例組;選取同一時(shí)期在承德市中心醫(yī)院體檢中心體檢的健康女性58例作為對(duì)照組。病例組于術(shù)前清晨抽取靜脈血,對(duì)照組于體檢日當(dāng)天清晨抽取靜脈血。兩組血清均及時(shí)離心提取上清液,將血清樣本貯存于-60℃的冰箱中,待樣本集齊后統(tǒng)一測(cè)量。應(yīng)用酶聯(lián)免疫吸附法(ELISA)分別測(cè)定兩組血清中MMP-9、EGF的表達(dá)水平。分別比較病例組與對(duì)照組中兩種因子的血清均值;考慮MMP-9、EGF的水平有可能受到子宮肌瘤的生長(zhǎng)位置、肌瘤的大小、月經(jīng)周期、肌瘤的病理類型等的影響,根據(jù)臨床病例資料,將病例組進(jìn)行組內(nèi)分組:①根據(jù)子宮肌瘤生長(zhǎng)位置的不同及所收集的病歷資料(術(shù)后病理回報(bào)結(jié)果分為粘膜下肌瘤及肌壁間肌瘤,漿膜下肌瘤少見),將病例組資料分為粘膜下肌瘤組和肌壁間肌瘤組;②根據(jù)B型超聲檢測(cè)肌瘤最大直徑6-133mm,取中位數(shù)57mm作為分界線,將病例組分為Dmax≤57mm組和Dmax57mm組;③根據(jù)患者處于不同月經(jīng)周期,將病例組分為卵泡期、黃體期及絕經(jīng)后期組;④根據(jù)病理回報(bào)的子宮肌瘤不同病理類型,將病例組分為富于細(xì)胞型肌瘤組及子宮平滑肌瘤組,對(duì)兩種因子血清學(xué)水平進(jìn)行組內(nèi)比較。統(tǒng)計(jì)分析采用SPSS17.0統(tǒng)計(jì)軟件進(jìn)行。所有數(shù)據(jù)均采用均數(shù)±標(biāo)準(zhǔn)差(X—±S)表示,多組數(shù)據(jù)間的比較采用單因素方差分析;兩組間比較應(yīng)用兩獨(dú)立樣本t檢驗(yàn),對(duì)兩組數(shù)據(jù)進(jìn)行方差齊性檢驗(yàn),方差齊者應(yīng)用t檢驗(yàn),方差不齊者應(yīng)用近似t檢驗(yàn)(t')檢驗(yàn)。以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1 MMP-9及EGF的血清表達(dá)水平在病例組和對(duì)照組中的比較病例組MMP-9及EGF血清平均水平與對(duì)照組相比明顯升高,P0.01。2不同生長(zhǎng)位置肌瘤MMP-9及EGF血清水平的比較粘膜下肌瘤組MMP-9和EGF血清水平比肌壁間肌瘤組明顯升高,差異具有顯著性,P0.05。3不同直徑子宮肌瘤MMP-9及EGF血清水平的比較Dmax≤57mm組MMP-9及EGF血清水平與Dmax57mm組的差異均無統(tǒng)計(jì)學(xué)意義,P0.05。4不同月經(jīng)周期患者血清MMP-9及EGF水平的比較卵泡期組MMP-9、EGF的血清均值與黃體期組沒有明顯差異(P0.05);絕經(jīng)后期組與非絕經(jīng)期組相比,兩組MMP-9、EGF水平差異不具有顯著性(P0.05)。5不同病理類型的子宮肌瘤患者血清MMP-9、EGF水平的比較富于細(xì)胞型子宮肌瘤組與普通子宮平滑肌瘤組血清MMP-9及EGF水平均無明顯差異(P0.05)。6經(jīng)相關(guān)性分析,血清MMP-9與EGF之間存在正相關(guān)。結(jié)論:1子宮肌瘤患者血清MMP-9、EGF水平均比對(duì)照組明顯升高,表明MMP-9及EGF可能參與子宮肌瘤的發(fā)病過程。2此兩項(xiàng)指標(biāo)對(duì)子宮肌瘤的診斷有一定的參考價(jià)值,且與患者的月經(jīng)周期沒有明顯的相關(guān)性。3此兩項(xiàng)指標(biāo)對(duì)鑒別子宮肌瘤生長(zhǎng)位置可以提供一定的血清學(xué)參考。4血清MMP-9和EGF水平可能不適合作為判斷子宮肌瘤大小的臨床監(jiān)測(cè)指標(biāo)。5血清MMP-9與EGF表達(dá)水平呈正相關(guān),表明這兩種因子在子宮肌瘤的發(fā)病中可能存在協(xié)同作用。
[Abstract]:Myoma of uterus (uterine myoma, UM (uterine): uterine leiomyoma leiomyoma, UL), also known as uterine fibroids (uterine, fibroid, UF) is the most common gynecological clinical female genital benign tumor. According to statistics, over 30 years old women of childbearing age are about more than 20% people suffering from uterine fibroids, the peak prevalence of female uterine fibroids in China between 41-50 years old, the age group prevalence rate is about 54.9%. because most of the uterine fibroids little or no symptoms, so the clinical survey reported the incidence rate may be much lower than its true incidence. And with the development of society and the change of the living environment, the pathogenesis of uterine leiomyoma the rate is gradually increased, and the age of onset tended to be younger. At this stage, the pathogenesis of uterine leiomyoma is still not completely clear, its pathogenesis and etiology is multi factor, multi link. A number of studies show that, in addition to Estrogen, progesterone, uterine fibroids, and also the development of matrix metalloproteinases (MMPs) and a variety of growth factors are closely related. There are reports, uterine fibroids may contribute to the formation of extracellular matrix (ECM) formation and accumulation to a certain extent, while MMPs is an important family in the degradation of extracellular matrix. The MMP-9.MMP-9 is an important member of MMPs family play degradation and remodeling in a Gelatinase in substrate, it is an important component of type IV -- form the basement membrane and extracellular matrix collagen. Recent studies indicate that MMP-9 and many kinds of gynecological benign and malignant diseases are closely related. Zhou Xiuping found through research MMP-9 the level of uterine leiomyoma cells increased significantly, may have a certain relationship with the occurrence of uterine fibroids. Reported effects of estrogen on uterine leiomyoma is indirect, it is a growth factor for intermediary factor from The role of the growth factor. Mainly include epidermal growth factor (EGF), transforming growth factor beta (TGF- beta), insulin-like growth factor (IGF), basic fibroblast growth factor (B FGF) and platelet-derived growth factor (PDGF). The study found that estrogen can produce EGF by stimulation estrogen responsive cells, EGF and EGFR were up-regulated, which involved in the pathogenesis of uterine leiomyoma. Through the study of serum matrix metalloproteinase 9 in patients with uterine leiomyoma (MMP-9) and epidermal growth factor (EGF) levels were measured to investigate the correlation between the expression level of MMP-9 and EGF and uterine myoma. Objective: through this experiment collected from patients with uterine fibroids (case group) and healthy subjects (control group), the determination of serum matrix metalloproteinase two serum -9 (MMP-9), epidermal growth factor (EGF) expression levels, the two factors in the case group and the control group in the blood Clear by comparing the mean; according to different clinical data, serum level of different types of uterine myoma were compared within the group, and then discuss the two kinds of serum cytokines expression and correlation between the level of uterine leiomyoma, and whether it can be used as a clinical detection index of uterine leiomyoma. Methods: 2013.01~2014.01 in the center of Chengde hospital surgical treatment, postoperative pathology in return for uterine myoma, 62 cases as cases and no other complications were selected; in the same period of healthy female medical examination center of Chengde Central Hospital in 58 cases as control group. Patients in the preoperative venous blood in the morning, the control group on the examination day morning venous blood two. The serum was centrifuged to extract supernatant promptly, serum samples stored in the refrigerator will be -60 DEG C, the sample set of Qi unified measurement. The application of enzyme linked immunosorbent assay (ELI SA) MMP-9 two in serum were measured, the expression level of EGF. Two factors were compared the mean serum groups and control group; consider MMP-9, EGF level of growth position is uterine myoma, leiomyoma size, menstrual cycle, effect of fibroids pathological types, according to the clinical data the group, group group according to the different position of uterine leiomyoma and collected medical records (postoperative pathological results divided into submucous myoma and intramural myoma, subserous myoma, rare) patients were divided into submucous myoma and intramural myoma group II; according to the B type ultrasonic detection of myoma of maximum diameter of 6-133mm, taking the median 57mm as the dividing line, the patients were divided into Dmax 57mm group and Dmax57mm group; according to the patients in different menstrual cycle, the patients were divided into the follicular phase and luteal phase and postmenopause According to the pathology group; uterine fibroids of different pathological types, the patients were divided into highly cellular leiomyoma of uterus myoma group and the group of two factor serum levels compared. Statistical analysis using SPSS17.0 statistical software. All the data were the mean standard deviation (X + S) said by comparison, multiple sets of data between the single factor variance analysis; comparison between the two groups using two independent samples t test, variance test on the data of the two groups using t test, variance Qi, the heterogeneity of variance using approximate t test (t') test with P0.05. Results: the difference was statistically significant. 1 serum MMP-9 and the expression level of EGF in the case group and the control group in the cases of group MMP-9 and average serum levels of EGF compared with the control group increased significantly, compared with different growth location of fibroids MMP-9 mucosal P0.01.2 and EGF serum levels of myoma group MMP-9 And the serum level of EGF was significantly higher than the intramural myoma group, the difference was significant, P0.05.3 uterine fibroids MMP-9 different diameter and EGF serum level of Dmax is less than or equal to 57mm group MMP-9 and the serum levels of EGF and Dmax57mm group had no significant difference, P0.05.4 different menstrual cycle in patients with serum MMP-9 and EGF levels between the follicular phase group MMP-9, EGF and mean serum luteal phase group did not differ significantly (P0.05); postmenopause group compared with the non menopausal group, two groups of MMP-9, EGF levels were not statistically significant (P0.05.5) of different pathological types of uterine leiomyoma patients serum MMP-9, EGF levels were not significantly different compared with the cell type of uterus myoma group and normal uterine leiomyoma group serum MMP-9 and EGF levels (P0.05.6) by correlation analysis, there was a positive correlation between the serum levels of MMP-9 and EGF. Conclusion: 1 the uterine myoma patients serum MMP-9, EGF levels were significantly higher than that of control That group was significantly increased, there is a certain reference value for.2 MMP-9 and EGF may be involved in the pathogenesis of uterine myoma of the two indexes in the diagnosis of uterine leiomyomas, no obvious correlation between.3 of the two index in differential diagnosis of uterine leiomyoma position can provide certain reference.4 serological serum MMP-9 and EGF levels may not be suitable as a judge of uterus the size of the fibroids clinical monitoring indexes of serum.5 MMP-9 and EGF expression levels were positively correlated with the patient's menstrual cycle, that may be the two factor in the pathogenesis of uterine fibroids have a synergistic effect.

【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R737.33

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