子宫肌瘤患者血清MMP-9、EGF水平及相关性研究

发布时间：2018-01-16 23:10

本文关键词：子宫肌瘤患者血清MMP-9、EGF水平及相关性研究　出处：《承德医学院》2015年硕士论文　论文类型：学位论文

更多相关文章： 子宫肌瘤 MMP-9 EGF 血清学 相关性

【摘要】：子宫肌瘤(uterine myoma,UM)即子宫平滑肌瘤(uterine leiomyoma,UL),又被称为子宫纤维瘤(uterine fibroid,UF),是临床妇科最常见的女性生殖器良性肿瘤。据统计,30岁以上的育龄期女性约有超过20%的人群患有子宫肌瘤,我国女性子宫肌瘤的患病高峰在41-50岁之间,此年龄段的患病率约为54.9%。因为大多数的子宫肌瘤很少甚至根本没有症状,所以临床调查所报道的发病率可能远远低于其真正的发病率。且随着社会的发展及生活环境的变迁,子宫肌瘤的发病率正在逐渐升高,且发病年龄更趋于年轻化。现阶段,子宫肌瘤的发病机制仍尚未完全明了,其发病机理及病因是多因素、多环节的。多项研究表明,除雌、孕激素外,子宫肌瘤的发生、发展还与基质金属蛋白酶家族(MMPs)及多种生长因子有密切关系。有相关文献报道,子宫肌瘤形成可能与细胞外基质(ECM)的形成和蓄积有一定关系,而MMPs正是降解细胞外基质的重要家族,其中MMP-9则是MMPs家族中发挥降解与重构作用的重要成员。MMP-9是明胶酶中的一种,它的底物是构成基底膜和细胞外基质的重要成分--Ⅳ型胶原。近年研究表明,MMP-9与多种妇科良、恶性疾病密切相关。周秀萍等通过研究发现子宫肌瘤细胞中MMP-9水平显著增加,可能与子宫肌瘤的发生有一定关系。据文献报导,雌激素对子宫肌瘤的作用是间接的,它是以生长因子为中介因子而从中发挥作用的。主要的生长因子包括表皮生长因子(EGF)、转移生长因子-β(TGF-β)、胰岛素样生长因子(IGF)、碱性成纤维生长因子(b FGF)和血小板源性生长因子(PDGF)等。研究发现,雌激素可通过刺激雌激素反应细胞产生EGF,EGF与EGFR表达水平上调,从而参与子宫肌瘤的发病机制。本研究通过对子宫肌瘤患者血清中基质金属蛋白酶9(MMP-9)和表皮生长因子(EGF)水平的测定,探讨MMP-9和EGF的表达水平与子宫肌瘤的相关性。目的:本实验通过采集子宫肌瘤患者(病例组)及健康体检者血清(对照组),测定两组血清中基质金属蛋白酶-9(MMP-9)、表皮生长因子(EGF)的表达水平,将两种因子在病例组及对照组中的血清均值进行比较;根据不同临床病历资料,将不同类型的子宫肌瘤患者的血清水平进行组内比较,进而探讨这两种因子的血清表达水平与子宫肌瘤发生的相关性,及其是否可以作为子宫肌瘤的临床检测指标。方法:选取2013.01~2014.01在承德市中心医院行手术治疗,术后病理回报为子宫肌瘤,且无其他合并症的患者62例作为病例组;选取同一时期在承德市中心医院体检中心体检的健康女性58例作为对照组。病例组于术前清晨抽取静脉血,对照组于体检日当天清晨抽取静脉血。两组血清均及时离心提取上清液,将血清样本贮存于-60℃的冰箱中,待样本集齐后统一测量。应用酶联免疫吸附法(ELISA)分别测定两组血清中MMP-9、EGF的表达水平。分别比较病例组与对照组中两种因子的血清均值;考虑MMP-9、EGF的水平有可能受到子宫肌瘤的生长位置、肌瘤的大小、月经周期、肌瘤的病理类型等的影响,根据临床病例资料,将病例组进行组内分组:①根据子宫肌瘤生长位置的不同及所收集的病历资料(术后病理回报结果分为粘膜下肌瘤及肌壁间肌瘤,浆膜下肌瘤少见),将病例组资料分为粘膜下肌瘤组和肌壁间肌瘤组;②根据B型超声检测肌瘤最大直径6-133mm,取中位数57mm作为分界线,将病例组分为Dmax≤57mm组和Dmax57mm组;③根据患者处于不同月经周期,将病例组分为卵泡期、黄体期及绝经后期组;④根据病理回报的子宫肌瘤不同病理类型,将病例组分为富于细胞型肌瘤组及子宫平滑肌瘤组,对两种因子血清学水平进行组内比较。统计分析采用SPSS17.0统计软件进行。所有数据均采用均数±标准差(X—±S)表示,多组数据间的比较采用单因素方差分析;两组间比较应用两独立样本t检验,对两组数据进行方差齐性检验,方差齐者应用t检验,方差不齐者应用近似t检验(t')检验。以P0.05为差异有统计学意义。结果:1 MMP-9及EGF的血清表达水平在病例组和对照组中的比较病例组MMP-9及EGF血清平均水平与对照组相比明显升高,P0.01。2不同生长位置肌瘤MMP-9及EGF血清水平的比较粘膜下肌瘤组MMP-9和EGF血清水平比肌壁间肌瘤组明显升高,差异具有显著性,P0.05。3不同直径子宫肌瘤MMP-9及EGF血清水平的比较Dmax≤57mm组MMP-9及EGF血清水平与Dmax57mm组的差异均无统计学意义,P0.05。4不同月经周期患者血清MMP-9及EGF水平的比较卵泡期组MMP-9、EGF的血清均值与黄体期组没有明显差异(P0.05);绝经后期组与非绝经期组相比,两组MMP-9、EGF水平差异不具有显著性(P0.05)。5不同病理类型的子宫肌瘤患者血清MMP-9、EGF水平的比较富于细胞型子宫肌瘤组与普通子宫平滑肌瘤组血清MMP-9及EGF水平均无明显差异(P0.05)。6经相关性分析,血清MMP-9与EGF之间存在正相关。结论:1子宫肌瘤患者血清MMP-9、EGF水平均比对照组明显升高,表明MMP-9及EGF可能参与子宫肌瘤的发病过程。2此两项指标对子宫肌瘤的诊断有一定的参考价值,且与患者的月经周期没有明显的相关性。3此两项指标对鉴别子宫肌瘤生长位置可以提供一定的血清学参考。4血清MMP-9和EGF水平可能不适合作为判断子宫肌瘤大小的临床监测指标。5血清MMP-9与EGF表达水平呈正相关,表明这两种因子在子宫肌瘤的发病中可能存在协同作用。
[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.

【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.33

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