PARP-1及EMT标志物在子宫内膜异位症中的表达及意义

发布时间：2018-03-21 11:48

本文选题：子宫内膜异位症　切入点：聚腺苷二磷酸核糖聚合酶-1　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景和目的子宫内膜异位症(endometriosis,简称内异症)是指具有活性的子宫内膜腺体和间质在子宫腔被覆内膜及子宫肌层以外的部位出现、生长、浸润。内异症在组织学上是良性疾病,但却有增生、浸润、转移及复发等恶性生物学行为。现在更倾向于认为内异症是一种类肿瘤疾病[1]。目前关于内异症的发生机制理论较多,最广为接受的理论为种植学说,即随经血逆流的子宫内膜碎片,经过粘附、侵袭及新生血管形成,在异地种植生长。而异位内膜细胞的迁移和侵袭与上皮间质转化(epithelial-to-mesenchymaltransition,EMT)有关,但其中具体的调控机制仍不清楚。聚腺苷二磷酸核糖聚合酶 PARP-1[Poly(ADP-ribose)polymerase-1,PARP-1]是广泛存在于真核细胞中的核蛋白质酶,在DNA损伤后修复、细胞增殖分化调控、细胞凋亡、炎症、基因组的稳定方面发挥着重要的作用[2]。PARP-1在多种肿瘤组织中表达增高并且可以调控肿瘤的EMT过程。但是,PARP-1是否在内异症中表达及其与内异症EMT的关系目前国内外均未见相关报道。本研究拟通过检测PARP-1在子宫内膜异位症在位内膜、异位内膜组织和正常子宫内膜组织中的表达情况,探讨PARP-1与EMT相关标志物E-钙黏蛋白(E-cadherin)、波形蛋白(vimentin)及转录调控因子Snail在内异症在位内膜及异位内膜中表达的关系,来阐明PARP-1在内异症发病机制中的作用。方法:分别采用免疫组织化学法、实时荧光定量PCR(RT-PCR)法、Western blotting法检测PARP-1和EMT相关标志物E-cadherin、vimentin和Snail在子宫内膜异位症在位内膜、异位内膜和正常子宫内膜组织中的表达情况,并对PARP-1、E-cadherin、vimentin和Snail的表达水平进行Spearman等级相关分析。结果:1、PARP-1、vimentin及Snail在内异症在位内膜及异位内膜组织中的表达水平比在正常子宫内膜组织中的表达水平高(P均0.05),E-cadherin在内异症在位内膜及异位内膜组织中的表达水平比在正常子宫在位内膜组织中的表达水平低(P均0.05)。而内异症在位内膜和异位内膜组织中,PARP-1、E-cadherin、vimentin及Snail的表达差异没有统计学意义(P均0.05)。2、在正常内膜、内异症在位内膜、异位内膜组织中PARP-1、E-cadherin、vimentin及Snail的表达均与增殖期和分泌期无关(P均0.05)。3、PARP-1、E-cadherin、vimentin及Snail的表达与内异症rASRM临床分期有关(P0.05)。4、在内异症在位内膜、异位内膜组织中,PARP-1的表达均与E-cadherin的表达呈负相关,与vimentin及Snail的表达呈正相关。结论:PARP-1在子宫内膜异位症在位内膜、异位内膜组织中表达增高并与EMT相关标志物(E-cadherin,vimentin,Snail)有相关关系,PARP-1可能参与了内异症的EMT过程。
[Abstract]:Background and objective endometriosis (endometriosis) refers to the presence, growth and infiltration of active endometrial glands and stroma outside the endometrium and the myometrium. Endometriosis is a benign disease histologically. However, there are some malignant biological behaviors, such as proliferation, infiltration, metastasis and recurrence. We are more inclined to think that endometriosis is a kind of tumor disease [1]. There are many theories about the mechanism of endometriosis at present, and the most widely accepted theory is the theory of implantation. That is to say, the endometrial fragments following the blood reflux, after adhesion, invasion and angiogenesis, are implanted and grown in different places. The migration and invasion of ectopic endometrial cells are related to epithelial-to-mesenchymal transition (EMTT). But the specific regulatory mechanisms are still unclear. Polyadenosine diphosphate polymerase (PARP-1) is a riboprotease widely found in eukaryotic cells, which repair after DNA damage, regulate cell proliferation, differentiation, apoptosis and inflammation. The stability of genome plays an important role in [2]. The expression of PARP-1 is increased in many kinds of tumor tissues and can regulate the EMT process of tumor. But whether the expression of PARP-1 and its relationship with EMT are present both at home and abroad. This study was designed to detect PARP-1 in eutopic endometrium of endometriosis. To investigate the expression of PARP-1 in ectopic endometrium and normal endometrium, and to explore the relationship between expression of PARP-1 and E-cadherin (E-cadherin), vimentin (vimentin) and Snail, a transcription regulator, in ectopic endometrium and ectopic endometrium. Methods: the role of PARP-1 and EMT markers E-cadherin vimentin and Snail in eutopic endometrium of endometriosis was detected by immunohistochemical method and real-time fluorescence quantitative PCRRT-PCRmethod. The expression of ectopic endometrium and normal endometrium, The expression levels of PARP-1E-cadherinvimentin and Snail were analyzed by Spearman grade correlation. Results the expression levels of PARP-1vimentin and Snail in eutopic endometrium and ectopic endometrium were higher than those in normal endometrium. The expression levels of PARP-1E-cadherinvimentin and Snail in eutopic and ectopic endometrium were lower than those in normal eutopic endometrium (P < 0.05), but there was no significant difference in the expression of PARP-1E-cadherinvimentin and Snail in eutopic and ectopic endometrium. Both P and P were 0. 05 ~ 0. 2, in normal intima, The expression of PARP-1E-cadherinvimentin and Snail in eutopic endometrium and ectopic endometrium were not correlated with proliferative and secretory phase (P 0.05). The expression of PARP-1E-cadherinvimentin and Snail was related to rASRM clinical stage (P0.05.4), and the expression of PARP-1E-cadherinvimentin and Snail was related to the clinical stage of endometriosis, and the expression of PARP-1E-cadherinvimentin and Snail was not related to the eutopic endometrium. The expression of PARP-1 in ectopic endometrium was negatively correlated with the expression of E-cadherin, and positively correlated with the expression of vimentin and Snail. The expression of PARP-1 may be involved in the EMT process of endometriosis, and the expression of PARP-1 may be related to the expression of E-cadherin in ectopic endometrium.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.71

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