脑胶质瘤患者外周血Th17、Th22细胞的表达及意义
发布时间：2018-10-13 15:52
【摘要】：研究背景胶质瘤是颅内最常见的原发性恶性肿瘤,近年来其发病率有逐年上升的趋势,由于肿瘤侵犯脑实质,侵袭、转移能力强,复发率高,5年生存率极低。目前,国内外治疗胶质瘤的措施仍是以手术治疗为主,辅以放、化疗及其他综合治疗。以往由于血脑屏障的存在,脑一直被看做是一个免疫豁免器官,但现在随着神经系统免疫学研究的深入,人们发现免疫细胞可以通过血脑屏障,T细胞可在脑内活化,这为脑胶质瘤的免疫治疗提供了基础。Th17、Th22细胞是新近发现的CD4+T淋巴细胞群,其中Th17细胞主要分泌IL-17因子,RORC是其分化的特异性转录调控因子；Th22细胞主要分泌IL-22因子,AHR是其分化的特异性转录调控因子。最近研究发现,Th17、Th22细胞在自身免疫性疾病、感染性疾病、肿瘤、血液病中均有异常表达,二者参与上述疾病的发生与进展过程,但二者在脑胶质瘤中的表达及其作用的研究相对较少。研究目的通过研究脑胶质瘤患者外周血中Th17、Th22细胞比例的变化及二者的相关关系,检测外周血单个核细胞RORC mRNA及AHR mRNA的表达及血清中IL-22的浓度,旨在探究Th17、Th22细胞及其相关因子在脑胶质瘤中的表达情况,初步探讨其在脑胶质瘤发生发展中的作用。研究方法选取2014年7月至2015年8月山东大学第二医院神经外科接受治疗的34例胶质瘤患者为病例组,并按其病理类型分组,其中低级别组(WHO Ⅰ-Ⅱ)共17例,高级别组(WHO Ⅲ-Ⅳ)共17例,同期24例健康体检者为对照组,均收集其晨起空腹肘静脉全血。1.应用流式细胞术检测外周血中Th17、Th22细胞的表达比例,其中Thl7定义为CD4+IFN-γ-IL-17+, Th22定义为CD4+IFN-γ- IL-17- IL-22+,并分析二者的比例变化及其相关关系。2.采用Ficoll密度梯度离心法分离外周血单个核细胞,用Trizol法提取细胞中的总RNA,逆转录后用实时荧光定量逆转录聚合酶链反应(RT-PCR)技术检测外周血单个核细胞中RORC mRNA及AHRmRNA的表达水平。3.采用酶联免疫吸附分析(Enzyme linked immunosorbent assay, ELISA)检测血浆中Th22细胞相关因子IL-22的水平。研究结果1.与健康对照组相比,脑胶质瘤患者组外周血Th17细胞比例(占淋巴细胞)有升高趋势,但两组间差异无统计学意义(P0.05),且高级别组(WHOⅢ-Ⅳ级)与低级别组(WHO Ⅰ-Ⅱ级)之间的差异无统计学意义(P0.05)。2.与健康对照组相比,脑胶质瘤患者组外周血Th22细胞比例(占淋巴细胞)明显升高(P0.05),且高级别组升高程度明显高于低级别组(P0.05)。脑胶质瘤患者外周血Th17与Th22细胞的表达呈正相关关系(r=0.40,P=0.03),健康对照组二者表达无相关关系(P0.05)。3.与健康对照组比较,脑胶质瘤患者外周血单个核细胞RORC mRNA及AHR mRNA的表达水平升高不明显(P0.05；P0.05)；且高级别组与低级别组相比,这两种因子的表达差异不明显(P0.05；P0.05)。4.脑胶质瘤患者血浆IL-22水平比健康对照组明显升高(P0.05),但高级别组与低级别组组间差异不明显(P0.05)。研究结论1.脑胶质瘤患者外周血中存在Th22细胞及其相关因子IL-22的异常升高,外周血Th22细胞及IL-22的变化或可作为监测脑胶质瘤发病及进展的指标。2.脑胶质瘤患者Th17与Th22细胞明显相关,二者可能共同参与脑胶质瘤的发生与发展过程,并有可能发挥协同作用。
[Abstract]:Background glioma is the most common primary malignant tumor in the brain. In recent years, the incidence of glioma has been increasing year by year. Because of tumor invasion, invasion and metastasis ability is strong, the recurrence rate is high, and the 5-year survival rate is very low. At present, the treatment of glioma at home and abroad is still mainly operated by surgery, supplemented by radiotherapy, chemotherapy and other comprehensive treatment. In the past due to the existence of blood-brain barrier, brain has been regarded as an immune-immune organ, but with the in-depth study of nervous system immunology, it has been found that immune cells can be activated in the brain through the blood-brain barrier and T-cells, which provides the basis for the immunotherapy of glioma. Th17, Th22 cells are newly discovered CD4 + T lymphocyte populations, among which Th17 cells secrete IL-17 factor, RORC is the specific transcription regulation factor of its differentiation; Th22 cells secrete IL-22 factor mainly, and AHR is the specific transcription regulation factor of its differentiation. It has been found that Th17 and Th22 cells have abnormal expression in autoimmune diseases, infectious diseases, tumors and blood diseases, both of which are involved in the occurrence and progression of these diseases, but their expression and their role in gliomas are relatively few. Objective To investigate the changes of Th17 and Th22 cell ratios in peripheral blood of glioma patients and their correlation, and to detect the expression of RORC mRNA and AHR mRNA in peripheral blood mononuclear cells and the concentration of IL-22 in serum. The expression of Th22 cells and their associated factors in gliomas was studied, and the role of Th22 cells in the development of glioma was discussed. Methods 34 glioma patients treated with neurosurgery from July 2014 to August 2015 were selected as case group and grouped according to their pathological types. Among them, there were 17 cases in the lower group (WHO I-鈪，
本文编号：2269167
[Abstract]:Background glioma is the most common primary malignant tumor in the brain. In recent years, the incidence of glioma has been increasing year by year. Because of tumor invasion, invasion and metastasis ability is strong, the recurrence rate is high, and the 5-year survival rate is very low. At present, the treatment of glioma at home and abroad is still mainly operated by surgery, supplemented by radiotherapy, chemotherapy and other comprehensive treatment. In the past due to the existence of blood-brain barrier, brain has been regarded as an immune-immune organ, but with the in-depth study of nervous system immunology, it has been found that immune cells can be activated in the brain through the blood-brain barrier and T-cells, which provides the basis for the immunotherapy of glioma. Th17, Th22 cells are newly discovered CD4 + T lymphocyte populations, among which Th17 cells secrete IL-17 factor, RORC is the specific transcription regulation factor of its differentiation; Th22 cells secrete IL-22 factor mainly, and AHR is the specific transcription regulation factor of its differentiation. It has been found that Th17 and Th22 cells have abnormal expression in autoimmune diseases, infectious diseases, tumors and blood diseases, both of which are involved in the occurrence and progression of these diseases, but their expression and their role in gliomas are relatively few. Objective To investigate the changes of Th17 and Th22 cell ratios in peripheral blood of glioma patients and their correlation, and to detect the expression of RORC mRNA and AHR mRNA in peripheral blood mononuclear cells and the concentration of IL-22 in serum. The expression of Th22 cells and their associated factors in gliomas was studied, and the role of Th22 cells in the development of glioma was discussed. Methods 34 glioma patients treated with neurosurgery from July 2014 to August 2015 were selected as case group and grouped according to their pathological types. Among them, there were 17 cases in the lower group (WHO I-鈪，
本文编号：2269167
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