本文選題：子宮腺肌病 + Dusp6　； 參考：《山東大學(xué)》2014年碩士論文

【摘要】：背景 子宮腺肌病(adenomyosis, AM)是一種常見的良性婦科疾病,子宮內(nèi)膜組織向子宮肌層浸潤,引起子宮肌層的炎癥和增生反映,可引起周期性或非周期性的盆腔痛和不規(guī)則陰道流血。Multivariate分析表明子宮腺肌病的患病率和婦女的年齡、妊娠及盆腔子宮內(nèi)膜異位癥顯著相關(guān)。然而,其病因和發(fā)病機(jī)制目前尚不明確。 纖維生長因子-2(Fibroblast growth factor, FGF2)是最早被確認(rèn)的血管形成性生長因子之一,FGF2通過酪氨酸激酶受體(RTKs) FGFR1而激活一系列的細(xì)胞內(nèi)信號傳導(dǎo)通路,從而形成完整的FGF信號傳導(dǎo)通路：FGF2/MAPK/ERK1/2信號通路�；罨腅RKl/2最終調(diào)節(jié)多種細(xì)胞活性,包括基因表達(dá)、有絲分裂、細(xì)胞增殖、細(xì)胞存活與凋亡以及細(xì)胞分化等多種細(xì)胞生物效應(yīng)。近年研究證實,FGF通路的活性受多個負(fù)反饋抑制因子嚴(yán)密控制,例如特異性雙重磷酸酶6(Dual-specificity phosphatase6, Dusp6), Sproutys(SPRYs)和Sef(Similar expression to fgf genes),可以形成生理性的負(fù)反饋環(huán)以限制FGFs/MAPK/ERK1/2信號傳導(dǎo)通路的過度活化。 目的 以子宮腺肌病在位內(nèi)膜(實驗組)和正常子宮內(nèi)膜組織(對照組)為研究對象,通過檢測Dusp6, Sprouty4和Sef的蛋白及mRNA的組織定位及表達(dá)程度,探討Dusp6, Sprouty4和Sef在子宮腺肌病組織中的表達(dá)及其臨床意義。 方法 實驗組為因子宮腺肌病行子宮切除術(shù)標(biāo)本,經(jīng)病理檢查證實均為子宮腺肌病,共30例；對照組為因子宮平滑肌瘤行子宮切除術(shù)標(biāo)本,內(nèi)膜經(jīng)病理檢查證實均為正常內(nèi)膜,共29例,。應(yīng)用免疫組織化學(xué)SP法和原位雜交技術(shù)分別檢測各組織中Dusp6, Sprouty4和Sef的蛋白及mRNA的組織定位和表達(dá)強(qiáng)度,分析對比其差異。結(jié)果 對照組及實驗組子宮內(nèi)膜腺上皮細(xì)胞中,Dusp6, Sprouty4及Sef蛋白的免疫組化染色呈強(qiáng)陽性,且主要聚集在細(xì)胞漿中,間質(zhì)細(xì)胞著色很淺。腺上皮細(xì)胞的表達(dá)強(qiáng)度明顯大于間質(zhì)細(xì)胞,免疫組織化學(xué)陽性結(jié)果為出現(xiàn)淡黃色至棕黃色顆粒。Dusp6, Sprouty4及Sef蛋白在子宮腺肌病在位內(nèi)膜腺體細(xì)胞中的表達(dá)明顯低于正常子宮內(nèi)膜腺體細(xì)胞(P0.05)。對照組和實驗組,Dusp6, Sprouty4及Sef蛋白的表達(dá)水平在增生期與分泌期均無統(tǒng)計學(xué)差異(P0.05)。Dusp6, Sprouty4及Sef mRNA在子宮腺肌病在位內(nèi)膜的表達(dá)陽性率低于正常子宮內(nèi)膜腺體細(xì)胞(P0.01),其中,陽性信號主要位于腺上皮細(xì)胞胞漿,間質(zhì)細(xì)胞陽性細(xì)胞率較低。結(jié)論 1. FGF2/MAPK/ERK1/2信號通路的負(fù)調(diào)控因子Dusp6, Sprouty4和Sef的蛋白及mRNA在實驗組子宮腺肌病在位內(nèi)膜中的表達(dá)顯著低于對照組的正常子宮內(nèi)膜,這三個分子表達(dá)的下調(diào)很可能通過對FGF通路的調(diào)節(jié)對子宮腺肌病的發(fā)生發(fā)展起重要作用。 2. Dusp6, Sprouty4和Sef的蛋白及mRNA,在子宮腺肌病在位內(nèi)膜增生期與分泌期表達(dá)上無顯著統(tǒng)計學(xué)差異,正常子宮內(nèi)膜也是如此。Dusp6, Sprouty4和Sef的蛋白及mRNA的表達(dá)沒有隨雌孕激素周期性的改變,很可能不受雌孕激素的調(diào)節(jié)。
[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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R711.71

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 王凌,濮德敏,張萍,黎寧;基質(zhì)金屬蛋白酶-2,-9在子宮腺肌病的表達(dá)[J];中國組織化學(xué)與細(xì)胞化學(xué)雜志;2002年03期

2 韓燕華,周應(yīng)芳,鄭淑蓉;子宮腺肌病患者血管內(nèi)皮生長因子表達(dá)的研究[J];中華婦產(chǎn)科雜志;2002年09期

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本文編號：1781772