子宫腺肌病患者内膜组织中Dusp6，Sprouty4及Sef的表达缺失及其意义

发布时间：2018-04-21 09:02

本文选题：子宫腺肌病 + Dusp6　；参考：《山东大学》2014年硕士论文

【摘要】：背景子宫腺肌病(adenomyosis, AM)是一种常见的良性妇科疾病,子宫内膜组织向子宫肌层浸润,引起子宫肌层的炎症和增生反映,可引起周期性或非周期性的盆腔痛和不规则阴道流血。Multivariate分析表明子宫腺肌病的患病率和妇女的年龄、妊娠及盆腔子宫内膜异位症显著相关。然而,其病因和发病机制目前尚不明确。纤维生长因子-2(Fibroblast growth factor, FGF2)是最早被确认的血管形成性生长因子之一,FGF2通过酪氨酸激酶受体(RTKs) FGFR1而激活一系列的细胞内信号传导通路,从而形成完整的FGF信号传导通路：FGF2/MAPK/ERK1/2信号通路。活化的ERKl/2最终调节多种细胞活性,包括基因表达、有丝分裂、细胞增殖、细胞存活与凋亡以及细胞分化等多种细胞生物效应。近年研究证实,FGF通路的活性受多个负反馈抑制因子严密控制,例如特异性双重磷酸酶6(Dual-specificity phosphatase6, Dusp6), Sproutys(SPRYs)和Sef(Similar expression to fgf genes),可以形成生理性的负反馈环以限制FGFs/MAPK/ERK1/2信号传导通路的过度活化。目的以子宫腺肌病在位内膜(实验组)和正常子宫内膜组织(对照组)为研究对象,通过检测Dusp6, Sprouty4和Sef的蛋白及mRNA的组织定位及表达程度,探讨Dusp6, Sprouty4和Sef在子宫腺肌病组织中的表达及其临床意义。方法实验组为因子宫腺肌病行子宫切除术标本,经病理检查证实均为子宫腺肌病,共30例；对照组为因子宫平滑肌瘤行子宫切除术标本,内膜经病理检查证实均为正常内膜,共29例,。应用免疫组织化学SP法和原位杂交技术分别检测各组织中Dusp6, Sprouty4和Sef的蛋白及mRNA的组织定位和表达强度,分析对比其差异。结果对照组及实验组子宫内膜腺上皮细胞中,Dusp6, Sprouty4及Sef蛋白的免疫组化染色呈强阳性,且主要聚集在细胞浆中,间质细胞着色很浅。腺上皮细胞的表达强度明显大于间质细胞,免疫组织化学阳性结果为出现淡黄色至棕黄色颗粒。Dusp6, Sprouty4及Sef蛋白在子宫腺肌病在位内膜腺体细胞中的表达明显低于正常子宫内膜腺体细胞(P0.05)。对照组和实验组,Dusp6, Sprouty4及Sef蛋白的表达水平在增生期与分泌期均无统计学差异(P0.05)。Dusp6, Sprouty4及Sef mRNA在子宫腺肌病在位内膜的表达阳性率低于正常子宫内膜腺体细胞(P0.01),其中,阳性信号主要位于腺上皮细胞胞浆,间质细胞阳性细胞率较低。结论 1. FGF2/MAPK/ERK1/2信号通路的负调控因子Dusp6, Sprouty4和Sef的蛋白及mRNA在实验组子宫腺肌病在位内膜中的表达显著低于对照组的正常子宫内膜,这三个分子表达的下调很可能通过对FGF通路的调节对子宫腺肌病的发生发展起重要作用。 2. Dusp6, Sprouty4和Sef的蛋白及mRNA,在子宫腺肌病在位内膜增生期与分泌期表达上无显著统计学差异,正常子宫内膜也是如此。Dusp6, Sprouty4和Sef的蛋白及mRNA的表达没有随雌孕激素周期性的改变,很可能不受雌孕激素的调节。
[Abstract]:background
Adenomyosis (AM) is a common benign gynecologic disease. Endometrium infiltrates into the myometrium of the uterus and causes inflammation and proliferation of the myometrium. It can cause periodic or non periodic pelvic pain and irregular vaginal bleeding by.Multivariate analysis of the prevalence of adenomyosis and women's age and pregnancy. It is highly correlated with pelvic endometriosis. However, its etiology and pathogenesis are not yet clear.
-2 (Fibroblast growth factor, FGF2) is one of the earliest confirmed angiogenic growth factors. FGF2 activates a series of intracellular signaling pathways through the tyrosine kinase receptor (RTKs) FGFR1, thus forming a complete FGF signal transduction pathway: FGF2/MAPK/ERK1/2 signaling pathway. Activation ERKl/2 final modulation. A variety of cell activities, including gene expression, mitosis, cell proliferation, cell survival and apoptosis, and cell differentiation. Recent studies have confirmed that the activity of FGF pathway is tightly controlled by multiple negative feedback inhibitors, such as specific double phosphorylate 6 (Dual-specificity phosphatase6, Dusp6), Sproutys (SPRYs). And Sef (Similar expression to FGF genes) can form a physiological negative feedback loop to limit the excessive activation of FGFs/MAPK/ERK1/2 signal transduction pathway.
objective
The expression and clinical significance of Dusp6, Sprouty4 and Sef in the tissues of adenomyosis of uterus were investigated by detecting the tissue localization and expression of Dusp6, Sprouty4 and Sef proteins and mRNA by using the eutopic endometrium (experimental group) and the normal endometrium tissue (control group).
Method
The experimental group was treated with hysterectomy for adenomyosis, and it was confirmed by pathological examination that all 30 cases were adenomyosis. The control group was treated with hysterectomy for uterine leiomyoma, and the endometrium was confirmed to be normal endometrium through pathological examination. 29 cases were confirmed by pathological examination. SP and in situ hybridization were used to detect Du in each tissue. The protein localization and expression intensity of SP6, Sprouty4 and Sef proteins and mRNA were analyzed and compared.
In the endometrial gland epithelial cells of the control group and the experimental group, the immunohistochemical staining of Dusp6, Sprouty4 and Sef protein was strongly positive, and mainly concentrated in the cytoplasm. The staining of interstitial cells was very shallow. The expression intensity of the epithelial cells of the gland was obviously greater than that of the stromal cells. The results of the immunological positive of the immuno histochemistry appeared to be yellowish to brown yellow granules.Dusp6, S The expression of prouty4 and Sef protein in the eutopic endometrium cells of adenomyosis was significantly lower than that of normal endometrium cells (P0.05). The expression level of Dusp6, Sprouty4 and Sef protein in the control and experimental groups was not statistically different (P0.05).Dusp6, Sprouty4 and Sef mRNA were in the endometrium endometrium of adenomyosis. The positive rate of expression was lower than that of normal endometrium cells (P0.01). The positive signal was mainly located in the cytoplasm of the epithelial cells of the gland, and the positive cell rate of interstitial cells was low.
The negative regulatory factors of 1. FGF2/MAPK/ERK1/2 signaling pathway Dusp6, Sprouty4 and Sef protein and mRNA are significantly lower in the eutopic endometrium of adenomyosis of the experimental group than in the normal endometrium of the control group. The downregulation of these three molecular expressions is likely to play an important role in the development of the adenomyosis by the regulation of the FGF pathway.
The protein and mRNA of 2. Dusp6, Sprouty4 and Sef were not significantly different in the expression of eutopic endometrium and secretory phase in adenomyosis. The normal endometrium was also so.Dusp6 that the expression of protein and mRNA in Sprouty4 and Sef was not periodically changed with estrogen and progesterone, and it was likely not to be regulated by estrogen and progesterone.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.71

【参考文献】