TIPE2在慢性阻塞性肺疾病患者外周血单个核细胞中表达的研究

发布时间：2018-04-05 12:28

本文选题：慢性阻塞性肺疾病　切入点：TIPE2　出处：《山西医科大学》2012年硕士论文

【摘要】：研究目的慢性阻塞性肺疾病（chronic obstructive pulmonary diseases，COPD）是呼吸系统最常见的炎症性疾病之一，以肺部病变为主并可累及其他器官，严重威胁人类健康，但其确切的发病机制尚未完全阐明。近年来的研究表明，COPD以气道、肺实质和肺血管的慢性炎症为特征，同时伴随由肺泡巨噬细胞、T淋巴细胞、中性粒细胞和嗜酸性粒细胞等组成的复杂的免疫细胞网络的交互作用，参与COPD发生发展的多个环节，对其调节机制的研究将为揭示COPD发生的分子机制以及利用免疫手段干预COPD的防治奠定基础。TIPE2，肿瘤坏死因子a诱导的蛋白8-2 (Tumor necrosis factor-a induced protein-8-like 2)，是2008年报道的新型抗炎蛋白，选择性高表达于炎症组织和淋巴组织，负性调节机体固有免疫和适应性免疫应答，参与维持免疫稳态。TIPE2这一新的免疫应答负性调节因子是否参与COPD的发生，截止目前尚无报道。本课题的研究目的是通过检测COPD病人外周血单个核细胞（peripheral blood mononuclear cells，PBMCs）TIPE2 mRNA表达水平变化并在此基础上分析其表达水平与病人临床指标的相关性，初步探讨TIPE2在COPD发生过程中的作用，为进一步探讨COPD的发病机制提供实验和理论依据，为COPD的预防、临床治疗和转归提供新的潜在靶点。材料和方法从我院呼吸科筛选确诊为COPD的住院患者42例，同时挑选37例体检健康对照者，抽取静脉血，，用密度梯度离心法分离PBMCs，并保留血清。采用RT-PCR和实时荧光定量PCR法检测PBMCs TIPE2的表达水平，用ELISA法检测血清中肿瘤坏死因子a（TNF-a）、白细胞介素6（IL-6）的含量，由定量数据分析其直线相关关系。研究结果（1）COPD组常规肺功能测定（conventional pulmonary function test, cPFT）参数FEV1、FVC、FEV1/FVC和FEV1/pre与对照组相比明显降低（P0.05）,而吸烟指数明显高于对照组（P0.05）。（2）COPD组TIPE2 mRNA表达水平为4.50±1.04，而对照组TIPE2 mRNA表达水平为11.25±1.37，COPD组TIPE2表达水平明显低于对照组（P0.01）。（3）COPD组血清中炎性细胞因子TNF-a、IL-6含量分别为19.33±2.03 pg/ml和18.05±2.31 pg/ml，而对照组血清中炎性细胞因子TNF-a、IL-6含量分别为10.33±2.40 pg/ml和9.01±1.53，COPD组的含量明显高于对照组（P0.05）。（4）COPD组TIPE2的表达水平与血清中TNF-a、IL-6的水平均呈负相关关系，相关系数分别为r=-0.441和r=-0.377（P0.05），而对照组二者之间无明显相关性。结论 COPD患者PBMCs中TIPE2表达下降，且其表达水平与炎性细胞因子TNF-a、IL-6的含量呈负相关，TIPE2可能在COPD的发病中通过调节炎症介质的水平参与这一疾病过程。
[Abstract]:Research purposeChronic obstructive pulmonary disease (pulmonary) is one of the most common inflammatory diseases of the respiratory system. Pulmonary diseases mainly involve other organs, which seriously threaten human health, but the exact pathogenesis has not been fully elucidated.Recent studies have shown that COPD is characterized by chronic inflammation of the airway, pulmonary parenchyma and pulmonary vessels, and is accompanied by a complex network of immune cells composed of alveolar macrophages, T lymphocytes, neutrophils and eosinophils.To participate in the development of COPD in a number of links,The study of its regulatory mechanism will lay a foundation for revealing the molecular mechanism of COPD and interfering with the prevention and treatment of COPD by immunological means. TIPE2, TNF- 伪 -induced protein 8-2 or necrosis factor-a induced protein-8-like _ 2, is a novel anti-inflammatory protein reported in 2008.Highly expressed in inflammatory and lymphoid tissues, negative regulation of innate immune response and adaptive immune response is involved in the maintenance of immune homeostasis. TIPE2, a new negative regulatory factor of immune response, has not been reported to be involved in the occurrence of COPD.The purpose of this study was to explore the role of TIPE2 in the pathogenesis of COPD by detecting the expression of TIPE2 mRNA in peripheral blood mononuclear cells (PBMC mononuclear cells) of patients with COPD, and analyzing the correlation between the expression level of TIPE2 and the clinical indexes of the patients.To further explore the pathogenesis of COPD provides experimental and theoretical basis for the prevention of COPD, clinical treatment and outcome to provide a new potential target.Materials and methodsForty-two inpatients diagnosed as COPD were selected from respiratory department and 37 healthy controls were selected. Venous blood was extracted and separated by density gradient centrifugation and serum was preserved.RT-PCR and real-time fluorescence quantitative PCR were used to detect the expression of PBMCs TIPE2, and ELISA method was used to detect the content of tumor necrosis factor (TNF-a) and interleukin-6 (IL-6) in serum. The linear correlation was analyzed by quantitative data.Research resultsThe parameters of conventional pulmonary function test (FEV1FVCU FEV1 / FVC and FEV1/pre) in COPD group were significantly lower than those in control group (P 0.05), and the smoking index was significantly higher than that in control group (P 0.05).The expression level of TIPE2 mRNA was 4.50 卤1.04in the control group and 11.25 卤1.37 in the control group, which was significantly lower than that in the control group (P 0.01).There was a negative correlation between the expression of TIPE2 and the level of TNF-a IL-6 in serum, the correlation coefficients were r-0.441 and r-0.377n (P0.05), respectively, but there was no significant correlation between them in the control group.ConclusionThe expression of TIPE2 in PBMCs of COPD patients decreased, and its expression level was negatively correlated with the content of inflammatory cytokine TNF-afi-IL-6. TIPE2 may be involved in the pathogenesis of COPD by regulating the level of inflammatory mediators.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.9

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