本文選題：濕疹TSLP　切入點：IL-25　出處：《天津醫(yī)科大學》2012年碩士論文　論文類型：學位論文

【摘要】：目的：濕疹是由多種內(nèi)外因素引起的一種具有明顯滲出傾向的炎癥性皮膚病,隨著自然環(huán)境的惡化,濕疹的患病率和發(fā)病率有逐年增高的趨勢,濕疹嚴重影響了人們的生活質(zhì)量,造成了個人及社會的經(jīng)濟負擔,已成為中西醫(yī)學研究的熱點。目前多認為是在機體內(nèi)部因素如免疫功能異常、皮膚屏障功能障礙等基礎上,由多種內(nèi)外因素綜合作用的結果,免疫性機制如變態(tài)反應和非免疫性機制如皮膚刺激均參與發(fā)病過程。 現(xiàn)代醫(yī)學研究證實,Th細胞分化紊亂是濕疹發(fā)生的重要因素。在正常條件下,Th1/Th2細胞的免疫功能處于動態(tài)平衡狀態(tài),一旦這種平衡態(tài)打破,將無法維持正常的免疫功能,從而發(fā)生各種相關疾病。Th1/Th2分化失衡是機體免疫應答調(diào)節(jié)的關鍵環(huán)節(jié),與濕疹的發(fā)生、發(fā)展和轉歸有關。胸腺基質(zhì)淋巴細胞生成素(TSLP)、IL-25在Th1與Th2平衡中扮演著重要的角色。IL-25(IL-17E)是近十年來發(fā)現(xiàn)的IL-17家族的新成員之一,IL-25主要在機體接觸過敏原由Th2細胞、黏膜上皮細胞、嗜酸性粒細胞、嗜堿性粒細胞、肥大細胞等分泌,TSLP是一種類白細胞介素7(IL-7)細胞因子。研究發(fā)現(xiàn),在多種過敏性疾病(哮喘,特應性皮炎等)中都能檢測到TSLP水平的增加。目前濕疹治療主要是H1受體拮抗劑、糖皮質(zhì)激素等進行局部或全身藥物治療,上述藥物由于其副作用使其在應用于濕疹時受到了極大的限制。因此,急需開發(fā)新的安全有效的治療濕疹的藥物,白芍總苷(total glu—cosides of paeony,TGP)為炎癥免疫性疾病的治療發(fā)揮了重要作用,對免疫平衡有著良好的調(diào)節(jié)作用,因此,在治療免疫性疾病表現(xiàn)出良好的前景。 本課題擬從以下幾個方面對其具體機制進行進一步的探討： 1. TSLP、IL-25在濕疹患者與正常人之間的表達差異； 2.不同性別的濕疹患者TSLP、IL-25表達的差異； 3. TSLP、IL-25表達與EASI的相關性； 4.濕疹患者TSLP、IL-25與臨床的相關性； 5. TSLP、IL-25與IL-17、IL-23細胞因子之間的相關性； 6.應用白芍總苷前后濕疹患者PBMC中兩種細胞因子的變化。 通過以上幾個方面推測TSLP、IL-25在濕疹發(fā)病中可能存在的機理,為濕疹發(fā)病機制的闡明、病情活動性的檢測及藥物研發(fā)與濕疹疾病的治療等提供一定的理論依據(jù)。 方法：本實驗采用實時熒光定量逆轉錄.聚合酶鏈反應(real time revgrsc transcription-polymerase chain reaction)的方法,對80例濕疹患者和40例正常對照者及20例濕疹患者TGP用藥前后外周血單核細胞TSLP、IL-25mRNA的表達量進行分析,擴增所得到的產(chǎn)物經(jīng)4.0%瓊脂糖溴化乙錠凝膠電泳,在凝膠成像儀下攝像證實。按照EASI的評分標準對80例濕疹患者進行評分。利用統(tǒng)計學方法分析TSLP、IL-25的表達與EASI臨床及實驗室指標的相關性。 結果： 1.濕疹患者外周血單核細胞TSLP和IL-25mRNA水平明顯高于正常組 2.不同性別的濕疹患者外周血單核細胞TSLP、IL-25表達的差異性沒有統(tǒng)計學意義 3.濕疹患者TSLP、IL-25表達與EASI正相關 4.濕疹患者外周血單核細胞TSLP、IL-25水平嗜酸性粒細胞計數(shù)正相關,與淋巴細胞、年齡、血沉、白蛋白、球蛋白、血肌酐、和血小板計數(shù)之間無明顯相關關系。 5. TSLP與IL-25之間存在正相關關系,與IL-17、IL-23之間無明顯相關性。 6.應用白芍總苷后濕疹患者TSLP、IL-25水平較用藥前明顯下降,差異有統(tǒng)計學意義。 結論： 1.濕疹患者組PBMC中的TSLP、IL-25表達水平增高,提示TSLP、IL-25在濕疹發(fā)病機制中具有一定的意義。 2.濕疹患者PBMC中TSLP、IL-25的表達與EASI成正相關性,可以作為判斷濕疹患者活動性的指標。 3.濕疹患者TSLP和IL-25mRNA水平嗜酸性粒細胞計數(shù)之間呈明顯正相關性,因此嗜酸性粒細胞計數(shù)的變化可以作為推測濕疹患者嚴重度指數(shù)的指標,為濕疹的治療效果的判斷提供一定的指導。 4、應用白芍總苷后濕疹患者TSLP和IL-25的水平是降低的,EASI及DLQI均下降,證明白芍總苷治療濕疹的療效是確切的。
[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錛，

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