PD-1和Tim-3在口腔扁平苔藓中表达的初步研究

发布时间：2018-04-13 00:39

本文选题：口腔扁平苔藓 + 共抑制分子　；参考：《郑州大学》2017年硕士论文

【摘要】：背景口腔扁平苔藓(Oral lichen planus,OLP)是一种常见的发生于口腔黏膜的慢性炎症性疾病,其患病率较高,约为0.5%~4.0%。该病病因不明确,大多数的研究认为OLP是T淋巴细胞介导的自身免疫性疾病,但在OLP患者中免疫系统对T细胞的调节作用机制尚不明确。程序性死亡分子-1(Programmed death-1,PD-1)和T细胞免疫球蛋白粘蛋白分子-3(T cell immunoglobulin and mucin domain-containing molecule-3,Tim-3)是影响T细胞功能的重要免疫调节因子,当T细胞表面有共抑制分子PD-1或Tim-3表达时,T细胞的功能即被抑制。大量研究发现,PD-1、Tim-3在多种免疫相关疾病中呈现出异常表达,且与疾病的发生发展密些相关。因此,本文欲从PD-1和Tim-3出发,进一步研究其在OLP发病机制中的作用。目的通过检测共抑制分子PD-1和Tim-3在OLP组织和正常口腔黏膜组织中的表达情况,探讨PD-1、Tim-3在OLP发生发展中作用和临床意义,为进一步深入了解OLP的发病机制,以及OLP患者的免疫靶向治疗提供理论依据。方法选取2014年10月至2016年10月期间,在郑州大学第一附属医院病理档案室存档的经临床和组织病理诊断为OLP的60例蜡块作为实验组,在河南省口腔医院口腔颌面外科收集的30例正常口腔黏膜组织作为对照组。通过免疫组织化学的方法检测PD-1和Tim-3在OLP组织和正常口腔黏膜组织的表达情况,分析PD-1和Tim-3与OLP患者的临床病理特征之间的关系,以及两者在OLP组织中表达情况的相关性分析。使用SPSS 23.0软件对各组数据进行统计学分析,PD-1和Tim-3在OLP组织和正常口腔黏膜组织中表达的差异及OLP不同临床病理特征间PD-1和Tim-3阳性表达率的比较使用χ~2检验,PD-1和Tim-3在OLP组织中表达的相关性分析采用Spearman相关分析。检验水准α=0.05,P0.05即差异具有显著性统计学意义。结果1.免疫组织化学结果显示:PD-1主要表于OLP组织的黏膜固有层,Tim-3主要表达于OLP组织的鳞状上皮层和黏膜固有层。PD-1、Tim-3均定位于细胞质和细胞膜,以细胞质为主。2.PD-1在OLP组织中和正常口腔黏膜组织中的阳性表达率分别为65%(39/60)和26.7%(8/30),Tim-3在OLP组织中和正常口腔黏膜中的阳性表达率分别为85%(51/60)和20%(6/30),即PD-1、Tim-3在OLP组织中的阳性表达率均明显高于在正常口腔黏膜组织中的阳性表达率(χ~2=11.799,P=0.001;χ~2=36.388,P0.05)。3.PD-1在糜烂型和非糜烂型OLP组织中的阳性表达率分别为41.0%(9/22)和78.9%(30/38),Tim-3在糜烂型和非糜烂型OLP组织中的阳性表达率分别为68.2%(15/22)和94.7%(36/38),即PD-1、Tim-3在糜烂型OLP组织中的阳性表达率均明显低于在非糜烂型OLP组织中的阳性表达率(χ~2=8.862,P=0.003;χ~2=5.764,P=0.016)。4.Spearman相关分析发现,PD-1与Tim-3的表达水平呈正相关(r=0.279,P=0.031)。结论1.共抑制分子PD-1和Tim-3在OLP组织中的表达水平较正常口腔黏膜组织中显著升高,提示OLP病损局部T细胞处于功能抑制状态。2.共抑制分子PD-1和Tim-3的表达水平与OLP的活跃程度呈负相关,提示PD-1和Tim-3的表达水平与局部T细胞的功能状态密切相关。3.在OLP组织中,PD-1和Tim-3的表达水平呈正相关,提示PD-1、Tim-3在OLP组织中的共表达。4.PD-1和Tim-3可能为OLP的生物学标记物,是OLP的免疫治疗靶点。
[Abstract]:The background of oral lichen planus (Oral lichen, planus, OLP) is a common occurrence in the oral mucosa of chronic inflammatory diseases, the prevalence rate is about 0.5%~4.0%. high, the cause of this disease is not clear, most studies suggest that OLP is a T lymphocyte mediated autoimmune diseases, but the regulation mechanism of the immune response in OLP patients in the system of T cells is not clear. Programmed cell death -1 (Programmed death-1 PD-1) and T cell immunoglobulin mucin -3 (T cell immunoglobulin and mucin domain-containing molecule-3, Tim-3) is an important immune effect of T cell function regulation factor, when T cell surface CO inhibitory molecules or PD-1 the expression of Tim-3, the function of T cells were inhibited. The study found a large number of PD-1, Tim-3 in many immune related diseases showed abnormal expression, and with the development of the disease. Some related. Therefore, we want to Starting from the PD-1 and Tim-3, the further research of the pathogenesis of OLP in rats. Objective to investigate the expression of PD-1 by PD-1, detection of CO inhibitory molecules and Tim-3 in OLP tissues and normal oral mucosa, Tim-3 and clinical significance in the role in the development of OLP, in order to further understand the pathogenesis of OLP and immune the target of OLP patients to provide a theoretical basis for the treatment. Methods from October 2014 to October 2016 in the First Affiliated Hospital of Zhengzhou University record room archived by clinical and pathological diagnosis of 60 cases of OLP paraffin as the experimental group as the control group in the Henan provincial Stomatological Hospital of oral and maxillofacial surgery collected 30 cases of normal oral mucosa by. The immunohistochemical method to detect PD-1 and Tim-3 expression in OLP tissues and normal oral mucosa, clinical and pathological analysis of PD-1 and Tim-3 in patients with OLP The relationship between the characteristics, and the correlation between the expression of OLP in tissues. Using SPSS 23 software statistical analysis were used to analyze the data, the differential expression of PD-1 and Tim-3 in OLP tissues and normal oral mucosa and OLP in different clinical and pathological characteristics between PD-1 and Tim-3 positive expression were compared using X ~2 test, analysis correlation between expression of PD-1 and Tim-3 in OLP tissues by Spearman correlation analysis. A =0.05 level test, there were significant statistical difference P0.05. 1. results of immunohistochemical results showed that PD-1 mainly in lamina propria OLP tissue, squamous epithelium and lamina propria of.PD-1 Tim-3 was mainly expressed in the OLP organization. Tim-3 was localized in the cytoplasm and cell membrane in the cytoplasm, the positive expression of.2.PD-1 in OLP tissues and normal oral mucosa tissues were respectively 65% (39/60) and 26.7% (8/30 ), the positive expression of Tim-3 in OLP tissues and normal oral mucosa. The rate was 85% (51/60) and 20% (6/30), PD-1, Tim-3 positive expression in OLP tissues were significantly higher than the positive expression in normal oral mucosa tissues (x ~2=11.799, P=0.001 x ~2=; 36.388, P0.05) the positive expression of.3.PD-1 in erosive and non erosive OLP tissues were respectively 41% (9/22) and 78.9% (30/38), the positive expression of Tim-3 in erosive and non erosive OLP tissues were respectively 68.2% (15/22) and 94.7% (36/38), namely PD-1, positive expression of Tim-3 was in erosion type in the OLP organization were obviously lower than in non erosive OLP tissues (x ~2=8.862, P=0.003 x ~2=5.764,.4.Spearman; P=0.016) correlation analysis showed that PD-1 correlated with the expression level of Tim-3 was positively (r=0.279, P=0.031). Conclusion the expression level of PD-1 and Tim-3 1. co inhibitory molecules in the OLP organization Compared with normal oral mucosa increased significantly, suggesting that the degree of active OLP lesions of T cells in the expression level of OLP and immunosuppression of.2. inhibitory molecules PD-1 and Tim-3 negatively correlated with the expression level, function that PD-1 and Tim-3 and local T cells is closely related to.3. in OLP, PD-1 and Tim-3 the expression levels were positively correlated, suggesting that PD-1 and Tim-3 co expression in OLP tissues of.4.PD-1 and Tim-3 may be a biological marker of OLP, is the target for immunotherapy of OLP.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R781.5

【相似文献】