TSLP和IL-25在湿疹患者中的表达及其临床意义

发布时间：2018-03-20 01:19

  本文选题：湿疹TSLP　切入点：IL-25　出处：《天津医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：湿疹是由多种内外因素引起的一种具有明显渗出倾向的炎症性皮肤病,随着自然环境的恶化,湿疹的患病率和发病率有逐年增高的趋势,湿疹严重影响了人们的生活质量,造成了个人及社会的经济负担,已成为中西医学研究的热点。目前多认为是在机体内部因素如免疫功能异常、皮肤屏障功能障碍等基础上,由多种内外因素综合作用的结果,免疫性机制如变态反应和非免疫性机制如皮肤刺激均参与发病过程。 现代医学研究证实,Th细胞分化紊乱是湿疹发生的重要因素。在正常条件下,Th1/Th2细胞的免疫功能处于动态平衡状态,一旦这种平衡态打破,将无法维持正常的免疫功能,从而发生各种相关疾病。Th1/Th2分化失衡是机体免疫应答调节的关键环节,与湿疹的发生、发展和转归有关。胸腺基质淋巴细胞生成素(TSLP)、IL-25在Th1与Th2平衡中扮演着重要的角色。IL-25(IL-17E)是近十年来发现的IL-17家族的新成员之一,IL-25主要在机体接触过敏原由Th2细胞、黏膜上皮细胞、嗜酸性粒细胞、嗜碱性粒细胞、肥大细胞等分泌,TSLP是一种类白细胞介素7(IL-7)细胞因子。研究发现,在多种过敏性疾病(哮喘,特应性皮炎等)中都能检测到TSLP水平的增加。目前湿疹治疗主要是H1受体拮抗剂、糖皮质激素等进行局部或全身药物治疗,上述药物由于其副作用使其在应用于湿疹时受到了极大的限制。因此,急需开发新的安全有效的治疗湿疹的药物,白芍总苷(total glu—cosides of paeony,TGP)为炎症免疫性疾病的治疗发挥了重要作用,对免疫平衡有着良好的调节作用,因此,在治疗免疫性疾病表现出良好的前景。 本课题拟从以下几个方面对其具体机制进行进一步的探讨： 1. TSLP、IL-25在湿疹患者与正常人之间的表达差异； 2.不同性别的湿疹患者TSLP、IL-25表达的差异； 3. TSLP、IL-25表达与EASI的相关性； 4.湿疹患者TSLP、IL-25与临床的相关性； 5. TSLP、IL-25与IL-17、IL-23细胞因子之间的相关性； 6.应用白芍总苷前后湿疹患者PBMC中两种细胞因子的变化。 通过以上几个方面推测TSLP、IL-25在湿疹发病中可能存在的机理,为湿疹发病机制的阐明、病情活动性的检测及药物研发与湿疹疾病的治疗等提供一定的理论依据。 方法：本实验采用实时荧光定量逆转录.聚合酶链反应(real time revgrsc transcription-polymerase chain reaction)的方法,对80例湿疹患者和40例正常对照者及20例湿疹患者TGP用药前后外周血单核细胞TSLP、IL-25mRNA的表达量进行分析,扩增所得到的产物经4.0%琼脂糖溴化乙锭凝胶电泳,在凝胶成像仪下摄像证实。按照EASI的评分标准对80例湿疹患者进行评分。利用统计学方法分析TSLP、IL-25的表达与EASI临床及实验室指标的相关性。 结果： 1.湿疹患者外周血单核细胞TSLP和IL-25mRNA水平明显高于正常组 2.不同性别的湿疹患者外周血单核细胞TSLP、IL-25表达的差异性没有统计学意义 3.湿疹患者TSLP、IL-25表达与EASI正相关 4.湿疹患者外周血单核细胞TSLP、IL-25水平嗜酸性粒细胞计数正相关,与淋巴细胞、年龄、血沉、白蛋白、球蛋白、血肌酐、和血小板计数之间无明显相关关系。 5. TSLP与IL-25之间存在正相关关系,与IL-17、IL-23之间无明显相关性。 6.应用白芍总苷后湿疹患者TSLP、IL-25水平较用药前明显下降,差异有统计学意义。 结论： 1.湿疹患者组PBMC中的TSLP、IL-25表达水平增高,提示TSLP、IL-25在湿疹发病机制中具有一定的意义。 2.湿疹患者PBMC中TSLP、IL-25的表达与EASI成正相关性,可以作为判断湿疹患者活动性的指标。 3.湿疹患者TSLP和IL-25mRNA水平嗜酸性粒细胞计数之间呈明显正相关性,因此嗜酸性粒细胞计数的变化可以作为推测湿疹患者严重度指数的指标,为湿疹的治疗效果的判断提供一定的指导。 4、应用白芍总苷后湿疹患者TSLP和IL-25的水平是降低的,EASI及DLQI均下降,证明白芍总苷治疗湿疹的疗效是确切的。
[Abstract]:Objective: eczema is a kind of obvious exudation of inflammatory skin disease caused by a variety of internal and external factors, with the deterioration of the natural environment, the prevalence of eczema and the incidence rate increases year by year, eczema seriously affect people's quality of life, resulting in personal and social economic burden, has become a hot topic in Chinese and Western medical research. It is considered to be in the body's internal factors such as immune dysfunction, skin barrier dysfunction on the basis, by the combined effects of a variety of external and internal factors, immune mechanisms, such as allergic reaction and non immune mechanisms such as skin irritation are involved in pathogenesis.
Modern medical research confirmed that Th cell differentiation disorder is an important factor of eczema. Under normal conditions, the immune function of Th1/Th2 cells in a state of dynamic balance, once the equilibrium broken, will not be able to maintain normal immune function, resulting in.Th1/Th2 related disease differentiation imbalance is a key link of immune regulation, and eczema the occurrence, development and prognosis. Thymic stromal lymphopoietin (TSLP), IL-25 plays an important role in.IL-25 Th1 and Th2 balance (IL-17E) is a new member of the family of IL-17 found in the past ten years, mostly in the IL-25 contact allergens of Th2 cells, epithelial cells, eosinophilic neutrophils, basophils, mast cell secretion, TSLP is a species of interleukin 7 (IL-7) cytokines. The study found that, in a variety of allergic diseases (asthma, atopic dermatitis, etc.) Detected in all levels of TSLP increased. The treatment of eczema is the main antagonist of H1 receptor, glucocorticoid and other local or systemic drug treatment, the drug because of its side effects in the application are restricted to eczema. Therefore, it is urgent to develop a safe and effective drug for treating eczema of the new. Total glucosides of paeony (total Glu - cosides of paeony, TGP) plays an important role in the treatment of inflammatory autoimmune diseases, immune balance has a moderating effect on the good, therefore, in the treatment of autoimmune diseases showed good prospects.
This subject is to further discuss its specific mechanism from the following aspects:
1. TSLP, IL-25 expression difference between eczema patients and normal people.
2. the difference of TSLP and IL-25 expression in eczema of different sex;
3. TSLP, IL-25 expression and the correlation of EASI;
4. TSLP, IL-25 and clinical correlation in eczema patients;
5. TSLP, the correlation between IL-25 and IL-17, IL-23 cytokine;
6. the changes of two cytokines in the PBMC of patients with eczema before and after the use of total glucoside of paeony.
Through these aspects, we speculate the possible mechanism of TSLP and IL-25 in the pathogenesis of eczema, and provide a theoretical basis for the elucidation of the pathogenesis of eczema, the detection of disease activity, the development of drugs and the treatment of eczema.
Methods: this experiment used real-time fluorescence quantitative reverse transcription polymerase chain reaction (real time revgrsc transcription-polymerase chain reaction) method, after 80 cases of eczema patients and 40 normal controls and 20 cases of TGP patients with eczema treatment of peripheral blood mononuclear cells of TSLP, analyze the expression of IL-25mRNA, amplified by the obtained products by 4% agarose gel electrophoresis and ethidium bromide, imaging confirmed in gel imager. Wasassessed 80 cases of eczema patients in accordance with the standard for evaluation of EASI. TSLP analysis using statistical methods, the correlation between IL-25 expression and EASI clinical and laboratory parameters.
Result锛，

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