本文選題：白癜風 + γ-干擾素　； 參考：《南方醫(yī)科大學》2010年碩士論文

【摘要】： 白癜風是一種原發(fā)的、局限性或泛發(fā)性皮膚色素脫失癥,是由于皮膚和毛囊的黑素細胞的酪氨酸酶系統(tǒng)的功能減退、喪失而引起的。白癜風可能是由于遺傳素質(zhì)和免疫因素聯(lián)合作用所致的一種皮膚病,確切發(fā)病機制尚未完全闡明,最近研究表明：細胞免疫狀態(tài)的改變、自身免疫和細胞因子在白癜風發(fā)病過程中起著重要的作用。 目前認為初始CD4+輔助T細胞可分為4種細胞亞群,分別是Th1、Th2、Th17和調(diào)節(jié)T細胞(Tregs)。免疫系統(tǒng)可分為天然免疫和適應(yīng)性免疫兩大部分,天然免疫系統(tǒng)可對外來的細菌、病毒及腫瘤細胞提供快速、非特異性的免疫效應(yīng)。此外,天然免疫對決定適應(yīng)性免疫應(yīng)答的強度上也起著重要作用。天然免疫系統(tǒng)由抗原遞呈細胞(APC)、單核巨噬細胞、樹突狀細胞(DCs)和NK細胞組成,而適應(yīng)性免疫由輔助T淋巴細胞亞群組成,它可分為Th1和Th2,這兩類免疫系統(tǒng)共同參與調(diào)節(jié)體內(nèi)的免疫應(yīng)答。Th1細胞主要分泌γ-干擾素(IFN-γ)、腫瘤壞死因子.-α(TNF-α)、白細胞介素-2(IL-2)、IL-12等細胞因子,主要介導(dǎo)細胞免疫；Th2細胞主要分泌IL-4、IL-5、IL-10、IL-13等細胞因子,主要介導(dǎo)體液免疫。正常情況下Th1/Th2處于相對平衡狀態(tài),不同疾病可引起Th1/Th2漂移,而Th1/Th2漂移又反過來影響疾病本身的進展。Th17細胞是-類新的CD4+T細胞亞群,這類細胞除了能特異性的分泌IL-17A和IL-17F,它還能產(chǎn)生IL-6、IL-1β、IL-22等細胞因子。上述這些細胞因子均有強大的致炎效應(yīng),在類風濕性關(guān)節(jié)炎、銀屑病、炎癥性腸病中Th17細胞均發(fā)揮著重要作用,除此之外,過敏性疾病和哮喘的發(fā)病也與Th17細胞密切相關(guān)。Th17細胞作為新的CD4+T效應(yīng)T細胞亞群,具有獨立的分化和發(fā)育機制,轉(zhuǎn)化生長因子-β(TGF-β)和IL-6聯(lián)合作用促進其分化,IL-23促進其增殖和存活,Th1和Th2細胞因子及IL-27則抑制其分化。孤獨受體(RORγt)是控制其分化的轉(zhuǎn)錄因子。Th17細胞特異地產(chǎn)生的IL-17、IL-22等效應(yīng)因子,主要介導(dǎo)炎癥反應(yīng)、自身免疫性疾病等的發(fā)生和發(fā)展。IL-12和IL-23共享IL-12p40亞單位,為證明IL-23在疾病中的作用,人們比較IL-12p35和IL-23p19亞單位基因敲除小鼠與自身免疫性疾病發(fā)生的關(guān)系,當IL-12p35基因敲除后,對自身免疫性疾病的發(fā)生無明顯影響,而當IL-23p19基因敲除后,自身免疫性疾病的發(fā)生率明顯降低,疾病的嚴重程度也明顯減輕,同時Th17細胞減少,IL-17水平下降。調(diào)節(jié)T細胞為抑制性T細胞,是某些組成性表達CD25的CD4+T細胞。此類細胞可抑制性調(diào)節(jié)CD4+或CD8+T細胞活化與增殖,在免疫應(yīng)答中發(fā)揮調(diào)節(jié)作用。目前認為,CD4+CD25+調(diào)節(jié)T細胞來源于胸腺,也可由成熟的CD4+CD25調(diào)節(jié)T細胞在外周淋巴組織中接觸特異性抗原,或在免疫抑制因子作用下活化而形成,它具有免疫無能性和免疫抑制性兩大特征,它可通過細胞之間直接接觸的方式抑制其它效應(yīng)性免疫細胞的功能,是迄今為止發(fā)現(xiàn)的最重要的免疫抑制細胞。 目的： 白癜風的發(fā)病與免疫機制密切相關(guān),既往有學者對白癜風患者Th1和Th2細胞因子進行了研究,但結(jié)果并不一致,而對Th17細胞因子的研究,目前未見報道,故本研究從CD4+T細胞的三個細胞亞群Th1、Th2和Th17相關(guān)細胞因子入手進行分析,探討尋常型白癜風患者的免疫狀態(tài)及部分相關(guān)細胞因子在白癜風發(fā)病中的作用。 方法： 1.選取44例尋常型白癜風患者及40例健康對照,抽取外周血,分離血清采用ELISA方法檢測白癜風患者和正常對照組外周血中IFN-γ、IL-10和IL-17的水平。 2.分離外周血中的單個核細胞,應(yīng)用實時熒光定量PCR法對上述研究對象外周血單個核細胞的IL-17mRNA的相對含量進行檢測。 3.統(tǒng)計分析：用SPSS13.0統(tǒng)計軟件對所有試驗數(shù)據(jù)進行統(tǒng)計分析,不同分期的尋常型白癜風患者之間以及不同臨床類型的尋常型白癜風患者之間IFN-γ、IL-10、IL-17及IL-17mRNA水平的比較采用One-Way-ANOVA進行分析,計量資料采用均數(shù)±標準差表示,若方差齊,兩兩之間比較采用LSD法,若方差不齊,則采用近似F檢驗Welch法,兩兩比較則采用Dunnttt's T3法,各細胞因子的水平與疾病病程的相關(guān)性檢驗采用Pearson相關(guān)分析,均采用雙側(cè)檢驗,檢驗水準為α=0.05。 結(jié)果： 1. IFN-γ在不同分期、不同類型的患者之間均無顯著性差異(F=1.568,1.950；P=0.215,0.110),與疾病的病程也無相關(guān)性(r=0.083,P=0.242)。 2.IL-10在不同分期、不同類型的白癜風患者中有顯著性差異(F=38.884,17.906；P=0.000),基于方差分析的多種比較表明,IL-10在進展期顯著高于穩(wěn)定期,穩(wěn)定期顯著高于正常對照組。泛發(fā)性白癜風患者IL-10的水平顯著高于正常對照組(P0.05),而局限性白癜風IL-10的水平與正常對照組相比無顯著性差異(P0.05)。IL-10的水平與疾病的病程無相關(guān)性(r=0.090,P=0.126)。 3.IL-17在不同分期、不同類型的白癜風患者中有顯著性差異(F=27.487,13.698；P=0.000),基于方差分析的多種比較表明,IL-17在進展期顯著高于穩(wěn)定期,穩(wěn)定期顯著高于正常對照組。泛發(fā)性白癜風患者IL-17的水平顯著高于正常對照組(P0.05),而局限性白癜風IL-17的水平與正常對照組相比無顯著性差異(P0.05),IL-17的水平與疾病的病程無相關(guān)性(r=0.215,P=0.276)。 4. IL-17mRNA在不同分期、不同類型的白癜風患者中有顯著性差異(F=22.284,15.342；P=0.000),基于方差分析的多種比較表明,IL-17mRNA在進展期顯著高于穩(wěn)定期,穩(wěn)定期顯著高于正常對照組。泛發(fā)性白癜風患者IL-17mRNA的水平顯著高于正常對照組(P0.05),而局限性白癜風IL-17mRNA的水平與正常對照組相比無顯著性差異(P0.05)。IL-17mRNA的水平與疾病的病程無相關(guān)性(r=0.145,P=0.365)。 結(jié)論： 1 Th2型細胞因子IL-10在尋常型白癜風患者中顯著高于正常對照組,且進展期顯著高于穩(wěn)定期,泛發(fā)性高于正常對照組,但正常對照組與局限性比較,無顯著性差異,表明Th1/Th2在尋常型泛發(fā)性白癜風患者中存在失衡,Th2細胞因子水平占優(yōu)勢,IL-10可能參與了尋常型泛發(fā)性白癜風的發(fā)病過程,并與疾病進展有關(guān)。 2 Th17型細胞因子IL-17及IL-17mRNA的水平在尋常型白癜風患者中顯著高于正常對照組,且進展期顯著高于穩(wěn)定期,泛發(fā)性高于正常對照組,但正常對照組與局限性比較,無顯著性差異,表明IL-17可能參與了尋常型泛發(fā)性白癜風的發(fā)病過程,并與疾病進展有關(guān)。
[Abstract]:Vitiligo is a primary, localized or generalized dermatosis caused by the loss of the function of the tyrosinase system of the melanocytes of the skin and hair follicles. Vitiligo may be a skin skin disease caused by the combination of genetic and immune factors. The exact pathogenesis has not yet been fully elucidated. Studies have shown that changes in cellular immunity, autoimmune and cytokines play an important role in the pathogenesis of vitiligo.
It is believed that the initial CD4+ assisted T cells can be divided into 4 subgroups, namely, Th1, Th2, Th17 and T cells (Tregs). The immune system can be divided into two parts of natural and adaptive immunity. The natural immune system can provide fast and non specific immune effects to foreign bacteria, virus and tumor cells. In addition, the natural immune response is determined by natural immune system. It also plays an important role in the intensity of adaptive immune response. The natural immune system consists of antigen presenting cells (APC), mononuclear macrophages, dendritic cells (DCs) and NK cells. The adaptive immunity is composed of auxiliary T lymphocyte subsets, which can be divided into Th1 and Th2. These two kinds of immune systems participate in regulating the immune response.Th1 in the body. Cells mainly secrete interferon gamma (IFN- gamma), tumor necrosis factor. - alpha (TNF- alpha), interleukin -2 (IL-2), IL-12 and other cytokines, which mainly mediate cellular immunity; Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-10, IL-13 and other cytokines, mainly mediated by medium conductors. Under normal conditions, Th1/Th2 is in a relatively balanced state, and the different diseases can cause Th1/Th. 2 drifting, and the Th1/Th2 drift in turn affects the disease itself..Th17 cells are the new CD4+T cell subsets. In addition to the specific secretion of IL-17A and IL-17F, these cells can also produce cytokines such as IL-6, IL-1 beta, IL-22 and so on. These cytokines have strong inflammatory effects in rheumatoid arthritis, psoriasis, and inflammation. Th17 cells play an important role in symptomatic enteropathy. In addition to this, the pathogenesis of allergic diseases and asthma is also closely related to Th17 cells as a new CD4+T effect T cell subgroup, which has an independent differentiation and development mechanism. The combination of transforming growth factor beta (TGF- beta) and IL-6 promotes its differentiation, IL-23 promotes its proliferation and survival. Live, Th1 and Th2 cytokines and IL-27 inhibit their differentiation. The solitary receptor (ROR gamma T) is a specific transcription factor.Th17 cell that controls the differentiation of IL-17, IL-22 and other effects factors, which mainly mediate the occurrence of inflammatory reactions, autoimmune diseases, and the development of.IL-12 and IL-23 shared IL-12p40 subunits, in order to prove that IL-23 is in the disease. People compare the relationship between IL-12p35 and IL-23p19 subunit knockout mice with autoimmune diseases. When IL-12p35 knockout, there is no obvious effect on the occurrence of autoimmune diseases. When IL-23p19 knockout, the incidence of autoimmune diseases is significantly reduced, and the severity of the disease is significantly reduced, and Th 17 cells decrease and IL-17 level decreases. Regulating T cells as inhibitory T cells is a CD4+T cell that expresses CD25 in some constituent cells. This kind of cell can inhibit the activation and proliferation of CD4+ or CD8+T cells and play an regulatory role in the immune response. It is believed that CD4+CD25+ regulates T cells from the thymus and can also be regulated by mature CD4+CD25 for T fine. Cells are exposed to specific antigens in peripheral lymphoid tissue or activated by immunosuppressive agents. It has two major characteristics of immune incompetence and immunosuppression. It can inhibit the function of other effector cells through direct contact between cells. It is the most important immunosuppressive cell that has been found so far.
Objective:
The pathogenesis of vitiligo is closely related to the immune mechanism. Previous scholars have studied the Th1 and Th2 cytokines in vitiligo patients, but the results are not consistent, and the study of Th17 cytokine is not reported. Therefore, this study begins with the analysis of the three cell subgroups of CD4+T cells, Th1, Th2 and Th17 related cytokines. The immune status of vitiligo patients and the role of some related cytokines in the pathogenesis of vitiligo.
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