子宫腺肌病中人类白细胞抗原E的表达和意义

发布时间：2018-02-03 10:49

本文关键词： HLA-E 子宫腺肌病病理免疫抑制　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景子宫腺肌病(adenomyosis,AM)是妇科常见的良性疾病之一,多发生于生育期女性,且常与子宫内膜异位症和子宫肌瘤同时存在。子宫腺肌病发生的病理学基础是在子宫肌层中发现有活性的子宫内膜组织,包括腺体和间质,但其病因至今尚未明确。多数研究者认为,由于子宫内膜基底层细胞异位到子宫的肌层内,引起肌层增生肥大,导致了子宫腺肌病的发生。本病发病的高危因素有:多次妊娠及分娩、人工流产、剖宫产、盆腔炎症、高雌激素血症等。在子宫腺肌病的临床症状中,最常见是月经的改变和进行性加重的痛经,妇科检查时可发现子宫体积增大,质硬且存在压痛。子宫腺肌病带给患者最常见的疼痛是进行性加重的痛经,有的患者甚至会发生性交痛与不孕,而大约有35%的患者无任何临床症状。子宫腺肌病的诊断主要依据患者的临床表现以及体征,影像学手段可起到一定的参考意义,但是最终的确诊依据病理学检查。随着近年来,对子宫腺肌病病因研究的深入,国内外大量的文献表明,异常的免疫功能导致机体无法清除异位的子宫内膜,与本病的发病有着一定的相关性。人类白细胞抗原(human leukocyte antigen,HLA)基因定位于第6染色体的短臂上,其中HLA-I类分子又分为经典的HLA-I类分子(包括HLA-A、HLA-B、HLA-C)和非经典的HLA-I类分子(包括HLA-E、HLA-F、HLA-G等)两种。其中,HLA-E是一种非经典的HLA-I类分子,具有高度保守性的特点。HLA分子分为膜结合性HLA-E和可溶性 HLA-E(soluble human leukocryte antigen E,sHLA-E)两种。HLA-E 分子在正常组织细胞的表达机制及意义至今尚不明确。近些年,越来越多的实验室和临床研究证实,HLA-E蛋白表达的上调参与了肿瘤的发生发展过程中的免疫学改变。然而,在子宫腺肌病的众多研究之中,关于HLA-E蛋白的研究却少之又少。研究的目的在于探讨子宫腺肌病中HLA-E蛋白的表达,并研究其表达水平带来的科研与临床应用价值。目的检测子宫腺肌病患者的异位和在位内膜组织中HLA-E蛋白的表达情况,以及患者接受保留了双侧子宫动脉的子宫病灶切除和子宫成形术前后血清中sHLA-E的水平,分别与正常人群的子宫内膜组织中的HLA-E以及血清中的sHLA-E的表达情况相比较。通过分析其表达的差异,研究在免疫耐受方面HLA-E蛋白的表达对子宫腺肌病病灶的产生、发展存在的意义,并探讨这种意义所带来的科研与临床价值。方法采用免疫组织化学染色技术测定24例子宫腺肌病患者的异位内膜、在位内膜以及20例正常内膜组织中HLA-E蛋白的表达情况,并使用H-score评分系统对其表达情况进行评分;采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)测定24例子宫腺肌病患者术前和术后1个月血清中sHLA-E的表达情况,并与20例正常子宫内膜患者的血清检测结果进行比较。最终,以上两步所得的数据结果均用IBM spss Statistics 22软件进行统计学方面的处理、分析。结果1.免疫组织化学染色结果:HLA-E分子的表达主要位于组织细胞的细胞质及细胞膜。在正常子宫内膜组织中,HLA-E分子阴性表达,或微弱表达。在子宫腺肌病患者的异位和在位内膜腺上皮细胞中,HLA-E分子表达均呈阳性,但两者之间差异显著,并有统计学意义(p0.01),且两组数据之间相关性明显;HLA-E在子宫腺肌病病灶中异位的内膜腺上皮的表达水平,同样高于正常内膜中腺上皮细胞,两者之间的差异具有统计学意义(p0.01);同时,子宫腺肌病患者在位内膜的腺上皮细胞中HLA-E分子表达水平显著高于正常子宫内膜,有统计学差异(p0.01)。2.ELISA实验结果:与子宫内膜正常的对照组相比较,sHLA-E分子在子宫腺肌病组的外周血血清中呈高水平表达状态,并且两者之间的差异存在统计学意义(p0.01)。子宫腺肌病组在接受保留了双侧子宫动脉的子宫病灶切除和子宫成形术后,血清中sHLA-E分子表达水平较术前下降显著,存在统计学差异(p0.01)。结论和意义本实验通过两部分的实验结果,证实子宫腺肌病患者异位和在位内膜的腺上皮细胞中和血清中的HLA-E分子表达过高,而HLA-E分子表达的上调会导致异常的免疫学改变,推测HLA-E的高水平表达可能会导致机体对子宫腺肌病中异位的内膜组织产生免疫抑制,参与了子宫腺肌病的发生。
[Abstract]:The background of adenomyosis (adenomyosis, AM) is one of the most common gynecological benign diseases, mainly occurring in women of reproductive age, and often associated with endometriosis and uterine fibroids exist. Pathological adenomyosis foundation is found endometrial tissue activity in myometrium, including glands and stroma however, its etiology is still not clear. Most researchers believe that, due to the muscular layer of endometrial basal layer cells of ectopic to the uterus, cause muscle hypertrophy, leading to the occurrence of adenomyosis. Risk factors for the onset of the disease are: multiple pregnancy and childbirth, abortion, cesarean section, pelvic inflammation hyperestrinemia, etc. in the clinical symptoms of adenomyosis, the most common is the menstrual changes and progressive dysmenorrhea, gynecological examination can be found when the uterine volume increases, hard and tenderness of adenomyosis to patients. The most common pain is progressive dysmenorrhea, some patients even sexual intercourse pain and infertility, and about 35% of the patients without any clinical symptoms. The diagnosis of adenomyosis is mainly based on the patient's clinical manifestations and signs, imaging methods can play a certain reference significance, but the final diagnosis according to the pathology check. In recent years, the etiology of adenomyosis research, a large number of domestic and foreign literatures show that immune dysfunction cause the body unable to remove the ectopic endometrium, has a certain relevance with the pathogenesis of this disease. Human leukocyte antigen (human leukocyte, antigen, HLA) gene is located on the short arm of sixth the chromosome, which HLA-I molecules and HLA-I molecules into the classic (including HLA-A, HLA-B, HLA-C) and non classical class HLA-I molecules (including HLA-E, HLA-F, HLA-G) two. Among them, HLA-E is a The non classical class HLA-I molecules,.HLA molecules are highly conserved into membrane-bound HLA-E and soluble HLA-E (soluble human leukocryte antigen E, sHLA-E) expression mechanism in normal tissue cells and significance of two.HLA-E molecules is still not clear. In recent years, more and more experimental and clinical studies confirmed that HLA-E protein the upregulation of the expression involved in immunological changes during tumor development. However, in many studies of adenomyosis, studies on HLA-E protein is less and less. The purpose of the study is to investigate the expression of HLA-E protein in adenomyosis, and scientific research and clinical value of the expression level brings. Objective to detect the expression of HLA-E protein in patients with adenomyosis ectopic and eutopic endometrial tissues, and patients retained the bilateral uterine artery uterine lesion excision The level of sHLA-E in serum and uterine forming before and after operation, the expression of endometrial tissue and normal people respectively in HLA-E and sHLA-E in serum were compared. By analyzing the differences in their expression, expression of HLA-E protein in immune tolerance of adenomyosis lesions, the development of the meaning of existence, and this brings the discussion of research significance and clinical value of determination of ectopic endometrium. Methods 24 cases of patients with adenomyosis technique of immunohistochemical staining, HLA-E protein in eutopic endometrium and 20 cases of normal endometrial tissue in the expression situation, and use the H-score scoring system on the expression score; by enzyme-linked immunosorbent assay (enzyme-linked immunosorbent assay, ELISA) to determine the expression of 24 cases of adenomyosis patients preoperatively and 1 months of sHLA-E in serum, and 20 cases of normal endometrium of patients To compare the serum test results. Finally, the above two steps: data from the results using IBM SPSS Statistics 22 software for processing, statistical analysis. Results: 1. immunohistochemical staining of the cytoplasm and cell membrane HLA-E expression mainly located in cells. In normal endometrium, the expression of HLA-E negative or weak expression in patients with adenomyosis ectopic and eutopic endometrial glandular epithelial cells, the expression of HLA-E was positive, but significant differences, with statistical significance (P0.01), and the correlation between the data of the two groups significantly; the expression level of HLA-E in adenomyosis ectopic endometrial epithelial cells the same is higher than that of normal endometrial glandular epithelial cells, the difference was statistically significant between the two (P0.01); at the same time, HLA- of patients with adenomyosis eutopic endometrial glandular epithelial cells The E expression was significantly higher than that in normal endometrium, there were significant differences (P0.01).2.ELISA experimental results: the control group and the normal endometrium compared to the expression level was high sHLA-E in adenomyosis group peripheral blood serum, and the difference between the two had statistical significance (P0.01). Uterine gland in an myopathy retained the bilateral uterine artery and uterine uterus resection after angioplasty, sHLA-E expression decreased significantly in serum, there was significant difference (P0.01). The conclusion and significance of this experiment according to the experimental results of the two part, demonstrated that HLA-E molecules in adenomyosis eutopic and ectopic endometrial glandular epithelium cells in serum and the expression of HLA-E and high expression rates will lead to a change in the abnormal high level expression of immunology, suggesting that HLA-E may cause the body to adenomyosis The endometrium of the middle ectopic tissue produces immunosuppression and participates in the occurrence of adenomyosis.

【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

【相似文献】