MCT-β2、TGF-β1和ES在子宮內(nèi)膜息肉組織中的表達及意義
本文選題:子宮內(nèi)膜息肉 + 血管生成 ; 參考:《鄭州大學(xué)》2014年碩士論文
【摘要】:背景和目的 子宮內(nèi)膜息肉(Endometrial polyp, EP)是突出于子宮內(nèi)膜表面的贅生物,為常見的婦科良性疾病之一。EP可引起子宮異常出血,在生育期婦女主要表現(xiàn)為月經(jīng)過多、經(jīng)間期出血或不孕,在絕經(jīng)期婦女則表現(xiàn)為不規(guī)則出血。EP由腺體和間質(zhì)部分組成,息肉表面被覆上皮,腺體單純性增生或腺囊性增生,由少量致密的纖維結(jié)締組織、炎性細胞浸潤和管壁較厚的血管組成間質(zhì)部分。近年來,由于人們生活質(zhì)量的提高和宮腔鏡檢查的廣泛應(yīng)用,EP的發(fā)病率和檢出率逐年增高,影響著現(xiàn)代婦女的身心健康。目前,EP的發(fā)病機制尚未完全明確,其一重要病理特征為間質(zhì)中含厚壁血管,因此推測血管生成相關(guān)因子可能參與EP發(fā)生發(fā)展相關(guān)過程,影響病情進展,可能對EP的診斷及治療提供新的思路。 肥大細胞(MastCell,MC)來源于骨髓造血干細胞,是常見的一種免疫應(yīng)答細胞,被喻為“多功能細胞因子之源”。近年研究發(fā)現(xiàn)MC與多種依賴于血管新生的疾病發(fā)病有關(guān),MC可刺激血管內(nèi)皮細胞增殖和新生血管的生成,,該種作用主要是通過類胰蛋白酶(Mast Cell Tryptase,MCT)來完成,它是MC內(nèi)預(yù)先合成的具有活性的中性蛋白酶,可作為MC特異性的標志。MCT-β2是MC脫顆粒時主要釋放的蛋白酶,目前MC、MCT在EP中的表達情況國內(nèi)尚無文獻報道。 轉(zhuǎn)化生長因子-β1(TransformingGrowthFactor beta1,TGF-β1)是一類促進和調(diào)節(jié)血管生成的重要因子,TGF-β1可直接刺激血管內(nèi)皮細胞的增生、趨化和遷移,也可對血管內(nèi)皮生長因子(VEGF)等因子的誘導(dǎo)作用,促進新生血管的形成。它在促進細胞的增殖、細胞外基質(zhì)的沉積、血管的生成、炎細胞的浸潤及組織纖維化等過程中起著重要的作用。 內(nèi)皮抑素(Endostatin,ES)是已知的最強內(nèi)源性血管生成抑制因子,它可直接抑制血管內(nèi)皮細胞的增生,使其生長周期停滯,誘導(dǎo)其凋亡,還能抑制一些血管生長因子如VEGF、堿性成纖維細胞生長因子(bFGF)等引起的內(nèi)皮細胞增殖和遷移,并對基質(zhì)金屬蛋白酶(MMP)有刺激作用,降解細胞外基質(zhì),引起內(nèi)皮細胞的遷移。ES對非內(nèi)皮細胞是沒有抑制作用的。 為此,本文探討了MCT-β2、TGF-β1和ES在子宮內(nèi)膜息肉組織中的表達情況,分析這些因子相關(guān)性,推測它們與新生血管的形成之間的關(guān)系,對于了解EP的發(fā)病機制以及術(shù)后復(fù)發(fā)、抗血管生成的藥物治療提供一定的理論依據(jù)。 材料與方法 1.實驗分組 息肉組:選取2013年4月到10月期間在本院行宮腔鏡下子宮內(nèi)膜息肉電切術(shù)的45例子宮內(nèi)膜息肉患者的息肉組織。 正常內(nèi)膜組:選取因輸卵管性不孕行宮腔鏡檢查患者17例,征得本人同意后,鏡下取少量正常子宮內(nèi)膜組織,病理結(jié)果為增生期子宮內(nèi)膜。 2.實驗方法 利用免疫組化SP法檢測MCT-β2、TGF-β1、ES蛋白在子宮內(nèi)膜息肉組織和正常內(nèi)膜組織中的表達。 3.統(tǒng)計方法 實驗數(shù)據(jù)均輸入SPSS17.0軟件包進行統(tǒng)計學(xué)處理。MCT-β2、TGF-β1和ES蛋白在息肉組織和正常內(nèi)膜組織中的陽性表達率的比較采用χ2檢驗,因子之間的相關(guān)性分析采用2×2配對資料的關(guān)聯(lián)性分析。檢驗水準為α=0.05(雙側(cè))。 結(jié)果 1. MCT-β2蛋白在息肉組的陽性表達率高于正常內(nèi)膜組,差異有統(tǒng)計學(xué)意義(P0.05); 2. TGF-β1蛋白在息肉組的陽性表達率高于正常內(nèi)膜組,差異有統(tǒng)計學(xué)意義(P0.05); 3. ES蛋白在息肉組的陽性表達率表達高于正常內(nèi)膜組,差異有統(tǒng)計學(xué)意義(P0.05); 4. MCT-β2與TGF-β1蛋白在子宮內(nèi)膜息肉組織中的表達呈正相關(guān)(P0.05,r=0.327); 5. MCT-β2與ES蛋白在子宮內(nèi)膜息肉組織中的表達呈正相關(guān)(P0.05, r=0.485); 6. TGF-β1與ES蛋白在子宮內(nèi)膜息肉組織中無明顯的相關(guān)性(P㧐0.05)。 結(jié)論 1. MCT-β2作為MC的特異性標記物,在子宮內(nèi)膜息肉組織中高表達,推測MC可能參與了子宮內(nèi)膜息肉的血管生成,在息肉的組織增生過程中起著重要作用。 2. MCT-β2、TGF-β1在子宮內(nèi)膜息肉組織中呈高表達,二者呈正相關(guān)關(guān)系,共同促進血管新生以及子宮內(nèi)膜息肉的發(fā)生與發(fā)展。 3. ES在子宮內(nèi)膜息肉組織中呈高表達,且與MCT-β2的表達呈正相關(guān),可能與機體內(nèi)血管生成調(diào)節(jié)的代償作用有關(guān)。
[Abstract]:Background and purpose
Endometrial polyp (EP) is a neoplasm prominent on the surface of the endometrium. It is one of the common benign gynecologic diseases,.EP can cause abnormal bleeding of the uterus. In the childbearing period, the women are mainly characterized by excessive menstruation, interphase bleeding or infertility. In the menopause women, the abnormal bleeding is.EP from the gland and the interstitial part. The surface of polyps is covered with epithelium, simple hyperplasia of glands or cystic hyperplasia, a small amount of dense fibrous connective tissue, inflammatory cell infiltration and the thicker vascular wall of the tube. In recent years, the incidence and detection rate of EP have increased year by year because of the improvement of people's quality of life and the extensive application of hysteroscopy. Women's physical and mental health. At present, the pathogenesis of EP is not completely clear. One of the important pathological features is the thick wall blood vessels in the interstitial tissue. Therefore, it is suggested that the angiogenesis related factors may be involved in the process of EP development, which may affect the progress of the disease, and may provide new ideas for the diagnosis and treatment of EP.
MastCell (MC) is derived from bone marrow hematopoietic stem cells. It is a common immune response cell. It is known as "the source of multi-functional cytokines". In recent years, the study found that MC is related to a variety of diseases dependent on angiogenesis, and MC stimulates the proliferation of vascular endothelial cells and the generation of neovascularization. This effect is mainly through the class. Mast Cell Tryptase (MCT), which is an active neutral protease synthesized in MC, can be used as a marker of MC specificity,.MCT- beta 2 is a protease that is the main release of MC degranulation. At present, there is no literature on the expression of MC and MCT in EP.
Transforming growth factor - beta 1 (TransformingGrowthFactor beta1, TGF- beta 1) is an important factor in promoting and regulating angiogenesis. TGF- beta 1 can directly stimulate the proliferation, chemotaxis and migration of vascular endothelial cells, also induce vascular endothelial growth factor (VEGF) and other factors, and promote the formation of new blood vessels. It promotes cell proliferation. It plays an important role in the process of extracellular matrix deposition, angiogenesis, inflammatory cell infiltration and tissue fibrosis.
Endostatin (ES) is the strongest endogenous angiogenesis inhibitor known. It can inhibit proliferation of vascular endothelial cells directly, induce its growth cycle stagnation, induce its apoptosis, and inhibit the proliferation and migration of some vascular growth factors such as VEGF, basic fibroblast growth factor (bFGF) and so on. Metalloproteinase (MMP) stimulates the degradation of extracellular matrix and induces migration of endothelial cells..ES has no inhibitory effect on non endothelial cells.
Therefore, the expression of MCT- beta 2, TGF- beta 1 and ES in endometrium polyps is discussed, and the correlation between these factors is analyzed, and the relationship between them and the formation of new blood vessels is deduced to provide a theoretical basis for understanding the pathogenesis of EP, the recurrence of postoperative and antiangiogenic treatment.
Materials and methods
1. experimental grouping
Polyp group: from April 2013 to October, 45 patients with endometrial polyps underwent hysteroscopic endometrial polypectomy.
In the normal endometrium group, 17 patients were selected for hysteroscopy because of tubal infertility. With the consent of the endometrium, a small amount of normal endometrium was taken under the microscope, and the pathological results were the endometrium in the hyperplastic period.
2. experimental method
The expression of MCT- beta 2, TGF- beta 1 and ES protein in endometrial polyps and normal endometrium tissues was detected by immunohistochemical SP.
3. statistical methods
The experimental data were all entered into SPSS17.0 software package for statistical treatment of.MCT- beta 2. The positive rate of TGF- beta 1 and ES protein in polyp tissues and normal endometrium tissues was compared by x 2 test. Correlation analysis between factors was analyzed with 2 x 2 paired data. The test level was alpha =0.05 (bilateral).
Result
The positive expression rate of 1. MCT- 2 protein in polyp group was higher than that in normal endometrium group (P0.05).
The positive expression rate of 2. TGF- 1 protein in polyp group was higher than that in normal endometrium group (P0.05).
3. the positive expression rate of ES protein in polyp group was higher than that in normal endometrium group (P0.05).
4. there was a positive correlation between the expression of MCT- beta 2 and TGF- beta 1 protein in endometrial polyps (P0.05, r=0.327).
5. there was a positive correlation between the expression of MCT- 2 and ES protein in endometrial polyps (P0.05, r=0.485).
6. there was no significant correlation between TGF- beta 1 and ES protein in endometrial polyps (P? 0.05).
conclusion
1. MCT- beta 2, as a specific marker of MC, is highly expressed in endometrium polyps. It is presumed that MC may be involved in the angiogenesis of endometrium polyps and plays an important role in the proliferation of polyps.
2. MCT- beta 2 and TGF- beta 1 are highly expressed in endometrium polyps, and the two are positively related, which jointly promote angiogenesis and the occurrence and development of endometrial polyps.
3. ES was highly expressed in endometrial polyps and positively correlated with the expression of MCT- beta 2, which may be related to the compensatory effect of angiogenesis regulation in the body.
【學(xué)位授予單位】:鄭州大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R737.33
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