MCT-β2、TGF-β1和ES在子宫内膜息肉组织中的表达及意义

发布时间：2018-05-28 06:26

本文选题：子宫内膜息肉 + 血管生成　；参考：《郑州大学》2014年硕士论文

【摘要】：背景和目的子宫内膜息肉(Endometrial polyp， EP)是突出于子宫内膜表面的赘生物，为常见的妇科良性疾病之一。EP可引起子宫异常出血，在生育期妇女主要表现为月经过多、经间期出血或不孕,在绝经期妇女则表现为不规则出血。EP由腺体和间质部分组成，息肉表面被覆上皮，腺体单纯性增生或腺囊性增生，由少量致密的纤维结缔组织、炎性细胞浸润和管壁较厚的血管组成间质部分。近年来，由于人们生活质量的提高和宫腔镜检查的广泛应用，EP的发病率和检出率逐年增高，影响着现代妇女的身心健康。目前，EP的发病机制尚未完全明确，其一重要病理特征为间质中含厚壁血管，因此推测血管生成相关因子可能参与EP发生发展相关过程，影响病情进展，可能对EP的诊断及治疗提供新的思路。肥大细胞（MastCell，MC）来源于骨髓造血干细胞，是常见的一种免疫应答细胞，被喻为“多功能细胞因子之源”。近年研究发现MC与多种依赖于血管新生的疾病发病有关，MC可刺激血管内皮细胞增殖和新生血管的生成，，该种作用主要是通过类胰蛋白酶（Mast Cell Tryptase,MCT）来完成，它是MC内预先合成的具有活性的中性蛋白酶，可作为MC特异性的标志。MCT-β2是MC脱颗粒时主要释放的蛋白酶，目前MC、MCT在EP中的表达情况国内尚无文献报道。转化生长因子-β1（TransformingGrowthFactor beta1，TGF-β1）是一类促进和调节血管生成的重要因子，TGF-β1可直接刺激血管内皮细胞的增生、趋化和迁移，也可对血管内皮生长因子（VEGF）等因子的诱导作用，促进新生血管的形成。它在促进细胞的增殖、细胞外基质的沉积、血管的生成、炎细胞的浸润及组织纤维化等过程中起着重要的作用。内皮抑素(Endostatin，ES)是已知的最强内源性血管生成抑制因子，它可直接抑制血管内皮细胞的增生，使其生长周期停滞，诱导其凋亡，还能抑制一些血管生长因子如VEGF、碱性成纤维细胞生长因子（bFGF）等引起的内皮细胞增殖和迁移，并对基质金属蛋白酶（MMP）有刺激作用，降解细胞外基质，引起内皮细胞的迁移。ES对非内皮细胞是没有抑制作用的。为此，本文探讨了MCT-β2、TGF-β1和ES在子宫内膜息肉组织中的表达情况，分析这些因子相关性，推测它们与新生血管的形成之间的关系，对于了解EP的发病机制以及术后复发、抗血管生成的药物治疗提供一定的理论依据。材料与方法 1.实验分组息肉组：选取2013年4月到10月期间在本院行宫腔镜下子宫内膜息肉电切术的45例子宫内膜息肉患者的息肉组织。正常内膜组：选取因输卵管性不孕行宫腔镜检查患者17例，征得本人同意后，镜下取少量正常子宫内膜组织，病理结果为增生期子宫内膜。 2.实验方法利用免疫组化SP法检测MCT-β2、TGF-β1、ES蛋白在子宫内膜息肉组织和正常内膜组织中的表达。 3.统计方法实验数据均输入SPSS17.0软件包进行统计学处理。MCT-β2、TGF-β1和ES蛋白在息肉组织和正常内膜组织中的阳性表达率的比较采用χ2检验，因子之间的相关性分析采用2×2配对资料的关联性分析。检验水准为α=0.05（双侧）。结果 1. MCT-β2蛋白在息肉组的阳性表达率高于正常内膜组，差异有统计学意义(P0.05)； 2. TGF-β1蛋白在息肉组的阳性表达率高于正常内膜组，差异有统计学意义(P0.05)； 3. ES蛋白在息肉组的阳性表达率表达高于正常内膜组，差异有统计学意义(P0.05)； 4. MCT-β2与TGF-β1蛋白在子宫内膜息肉组织中的表达呈正相关（P0.05,r=0.327)； 5. MCT-β2与ES蛋白在子宫内膜息肉组织中的表达呈正相关（P0.05, r=0.485)； 6. TGF-β1与ES蛋白在子宫内膜息肉组织中无明显的相关性（P㧐0.05）。结论 1. MCT-β2作为MC的特异性标记物，在子宫内膜息肉组织中高表达，推测MC可能参与了子宫内膜息肉的血管生成，在息肉的组织增生过程中起着重要作用。 2. MCT-β2、TGF-β1在子宫内膜息肉组织中呈高表达，二者呈正相关关系，共同促进血管新生以及子宫内膜息肉的发生与发展。 3. ES在子宫内膜息肉组织中呈高表达，且与MCT-β2的表达呈正相关，可能与机体内血管生成调节的代偿作用有关。
[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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

【参考文献】