【摘要】：目的：玫瑰糠疹(pityriasis rosea, PR)是一種自限性的炎癥性皮膚病，病程一般為6-8周。臨床特征表現(xiàn)為黃紅色,圓形或橢圓形，與皮紋長軸一致的紅斑，其表面附有領(lǐng)圈樣脫屑，多發(fā)生于軀干及四肢近端。玫瑰糠疹病因及發(fā)病機制尚不清楚，目前多認(rèn)為與感染后誘發(fā)的細(xì)胞免疫失衡有關(guān)。 Th1細(xì)胞主要介導(dǎo)與細(xì)胞毒和局部炎癥有關(guān)的免疫應(yīng)答,參與細(xì)胞免疫應(yīng)答，Th2細(xì)胞的主要參與體液免疫應(yīng)答，刺激B細(xì)胞分化、增殖,并產(chǎn)生抗體。調(diào)節(jié)性T細(xì)胞(regulatory T cell,Treg)是一群具有免疫抑制和免疫調(diào)節(jié)功能的細(xì)胞,在機體維持免疫自穩(wěn)、介導(dǎo)體內(nèi)免疫耐受、以及防止自身免疫性疾病方面具有重要的作用。轉(zhuǎn)錄因子T-bet(T box expressed in Tcells)、GATA-3(GATA-binding protein-3)分別正調(diào)控Th1細(xì)胞、Th2細(xì)胞的發(fā)育,二者最終決定Th0向Th1/Th2的轉(zhuǎn)化。T-bet在Thl細(xì)胞分化中起著核心作用,它不僅控制Thl細(xì)胞特征性細(xì)胞因子(interferon, IFN)-γ的表達(dá)，而且誘導(dǎo)已定向的Th2細(xì)胞向相反的Thl細(xì)胞分化。GATA-3是Th2特異性轉(zhuǎn)錄因子，在轉(zhuǎn)錄水平調(diào)節(jié)Th2類細(xì)胞因子的表達(dá)，促進(jìn)Th2細(xì)胞特征性細(xì)胞因子(interleukin, IL)-4等的產(chǎn)生，限制Th1細(xì)胞的分化。Foxp3(forkhead／winged helix transcription factor)特異的表達(dá)于調(diào)節(jié)性T細(xì)胞，對Treg細(xì)胞的分化以及發(fā)揮生物學(xué)功能均起著重要的作用。 T-bet、GATA-3及Foxp3在Th細(xì)胞的分化中具有重要的作用。T-bet/GATA-3決定Th1/Th2極化分化的關(guān)鍵因素，國內(nèi)外的學(xué)者對T-bet/GATA-3在哮喘、炎癥性腸病等多種疾病中表狀況做了大量的研究工作。Foxp3介導(dǎo)Treg細(xì)胞的分化，大量的研究證實Foxp3與腫瘤、自身免疫性疾病、感染性疾病等有關(guān)。在本課題應(yīng)用實時熒光定量RT-PCR技術(shù)檢測檢測玫瑰糠疹患者在外周血單個核細(xì)胞(the peripheral bloodmononuclear cells，PBMC)中轉(zhuǎn)錄因子T-bet、GATA-3及Foxp3的mRNA的表達(dá)，通過探討Th1細(xì)胞、Th2細(xì)胞和Treg細(xì)胞分化的關(guān)鍵性轉(zhuǎn)錄因子T-bet、GATA-3及Foxp3表達(dá)狀況，分析其在玫瑰糠疹發(fā)病機制中所發(fā)揮的作用和意義及該病的免疫功能狀態(tài)。 方法：病例組;20例玫瑰糠疹患者；對照組：22例健康人群：病例組：均來自河北醫(yī)科大學(xué)第二醫(yī)院皮膚科門診，男12例，女8例。平均年齡：23.5歲，病程3天-2月，患者入選標(biāo)準(zhǔn)：⑴均有典型的臨床表現(xiàn)(表現(xiàn)黃紅色,圓形或橢圓形，與皮紋長軸一致的紅斑，其表面附有領(lǐng)圈樣脫屑)；⑵受試前臨床檢查無感染性疾病，無其他免疫相關(guān)性疾病，1個月內(nèi)無系統(tǒng)用藥史(未服用免疫抑制劑及激素、抗組胺藥)、無不安全性行為史。對照組：22例均無過敏性疾病、自身免疫性疾病及家族史的健康人群，其性別、年齡與病例組經(jīng)統(tǒng)計學(xué)分析，均無統(tǒng)計學(xué)差異。本研究采用SYBRGreen I實時熒光定量RT-PCR技術(shù)檢測病例組與對照組外周血單個核細(xì)胞中T-betmRNA、GATA-3mRNA和Foxp3mRNA的表達(dá)水平，實驗數(shù)據(jù)應(yīng)用SPSS13.0統(tǒng)計軟件分析，以試驗結(jié)果應(yīng)用(x±s)表示，并采用兩獨立樣本比較的t檢驗，P0.05有統(tǒng)計學(xué)意義。 結(jié)果：1實驗數(shù)據(jù)顯示T-bet mRNA RQ值，玫瑰糠疹組RQ值為0.83±0.57，健康對照組RQ值為0.52±0.36，，經(jīng)t檢驗，t值=2.055，P值=0.046，玫瑰糠疹患者組T-bet mRNA表達(dá)水平升高，兩組間差異有統(tǒng)計學(xué)意義(P0.05)。2實驗數(shù)據(jù)顯示GATA-3mRNA RQ值，玫瑰糠疹組RQ值為0.68±0.29，健康對照組RQ值為1.22±1.02，經(jīng)t檢驗，t值=2.363，P值=0.026，玫瑰糠疹患者組GATA-3mRNA表達(dá)水平降低，兩組間差異有統(tǒng)計學(xué)意義(P0.05)。3實驗數(shù)據(jù)顯示Foxp3mRNA RQ，玫瑰糠疹組RQ值為0.92±0.61，健康對照組RQ值為1.48±0.93，經(jīng)t檢驗，t值=2.267，P值=0.029，玫瑰糠疹患者組Foxp3mRNA表達(dá)水平降低，兩組間差異有統(tǒng)計學(xué)意義（P0.05）。 結(jié)論：玫瑰糠疹患者外周血單個核細(xì)胞T-bet mRNA表達(dá)水平升高，GATA-3mRNA表達(dá)水平降低，可能存在Th1細(xì)胞亞群的高表達(dá)，Th2細(xì)胞亞群的低表達(dá)。T-bet/GATA-3mRNA比率升高，Th1/Th2向Th1方向極化。提示玫瑰糠疹的發(fā)病過程是以Th1細(xì)胞占優(yōu)勢的細(xì)胞免疫為主的可能性極大。玫瑰糠疹患者外周血單個核細(xì)Foxp3mRNA降低，表明可能存在Treg細(xì)胞表達(dá)減少，其免疫抑制功能降低。轉(zhuǎn)錄因子T-bet、GATA-3、Foxp3均參與了玫瑰糠疹的發(fā)病過程。
[Abstract]:Objective: pityriasis rosea (PR) is a self limiting inflammatory dermatosis with a course of 6-8 weeks. The clinical features are yellow red, round or oval, red spots consistent with the long axis of the dermatosis, with a collar like desquamation on the surface, mostly in the trunk and proximal extremities. The etiology and pathogenesis of pityriasis rose is not clear, At present, it is believed that it is related to the imbalance of cellular immunity induced by infection.
Th1 cells mainly mediate immune responses associated with cytotoxic and local inflammation, participate in cellular immune responses, Th2 cells are mainly involved in humoral immune responses, stimulate B cells to differentiate, proliferate, and produce antibodies. Regulatory T cells (regulatory T cell, Treg) are a group of cells with immune suppression and immunomodulatory functions, and are maintained in the body. T-bet (T box expressed in Tcells) and GATA-3 (GATA-binding protein-3) regulate the development of Th1 cells and Th2 cells, respectively. The two of them ultimately determine the transformation of Th0 to play a core role in the differentiation of the cells. It is used not only to control the expression of the characteristic cytokine (interferon, IFN) - gamma of Thl cells, but also to induce the directed Th2 cells to differentiate into the opposite Thl cells, which are Th2 specific transcription factors, regulate the expression of Th2 cell factors at the transcriptional level, and promote the production of Th2 cell specific cytokine (interleukin, IL) -4 and so on. The differentiation of 1 cells (forkhead / winged helix transcription factor) is specifically expressed in the regulatory T cells, which plays an important role in the differentiation of Treg cells and the biological function of Treg cells.
T-bet, GATA-3 and Foxp3 play an important role in the differentiation of Th cells..T-bet/GATA-3 determines the key factors for polarization and differentiation of Th1/Th2. Scholars at home and abroad have done a lot of research on the status of T-bet/GATA-3 in asthma, inflammatory bowel disease and many other diseases,.Foxp3 mediated Treg cell differentiation, and a large number of studies have confirmed Foxp3 and tumor, The application of real time fluorescence quantitative RT-PCR technique to detect the detection and detection of mRNA of T-bet, GATA-3 and Foxp3 in peripheral blood mononuclear cells (the peripheral bloodmononuclear cells, PBMC) in this subject by real time fluorescence quantitative quantitative detection, and to explore the differentiation of Th1 cells, Th2 cells and cells. The expression of key transcription factors, T-bet, GATA-3 and Foxp3, and its role and significance in the pathogenesis of pityriasis rose and the immune function state of the disease.
Methods: case group, 20 cases of rosea pityriasis, control group: 22 healthy people: case group: all from the Department of Dermatology of the second hospital of Hebei Medical University, 12 men and 8 women. The average age is 23.5 years old, the course of disease is -2 months, the standard of admission: (1) all the typical clinical manifestations (rounded, round or oval, and skin length) Uninfected diseases, no other immune related diseases, no systematic history of drug use within 1 months (not taking immunosuppressive agents and hormones, antihistamines) and a history of safe behavior without any other immune related diseases. In the control group, 22 cases had no allergic diseases, autoimmune diseases and families. In the healthy population of history, there was no statistical difference between the sex, age and case group. The SYBRGreen I real-time fluorescence quantitative RT-PCR technique was used to detect the expression level of T-betmRNA, GATA-3mRNA and Foxp3mRNA in the peripheral blood mononuclear cells of the case group and the control group. The experimental data were analyzed by the SPSS13.0 statistical software. The results of the test were applied (x + s) and the t test of two independent samples was used. P0.05 had statistical significance.
Results: 1 the experimental data showed the value of T-bet mRNA RQ, the RQ value of the rosea pityriasis group was 0.83 + 0.57, the RQ value of the healthy control group was 0.52 + 0.36, the t test, t value =2.055, P =0.046, the T-bet mRNA expression level of the patients with pityriasis rose, the difference between the two groups was statistically significant, and the value of the rosea pityriasis group was 0.6. 8 + 0.29, the RQ value of the healthy control group was 1.22 + 1.02, t test, t value =2.363, P value =0.026, the GATA-3mRNA expression level in the patients with pityriasis rose, and the difference between the two groups was statistically significant (P0.05).3 experimental data showed Foxp3mRNA RQ, the RQ value of the rosea pityriasis group was 0.92 + 0.61, and the healthy Kang control group was 1.48 + 0.93. The expression level of Foxp3mRNA in patients with pityriasis rosea decreased, and the difference between the two groups was statistically significant (P0.05).
Conclusion: the expression level of T-bet mRNA in peripheral blood mononuclear cells of the patients with furfuronyriasis rose, the expression level of GATA-3mRNA decreased, the high expression of Th1 cell subsets may exist, the low expression of.T-bet/GATA-3mRNA in Th2 cell subsets increased and Th1/Th2 was polarized to Th1, suggesting that the pathogenesis of the rash is the dominant cells in Th1 cells. The possibility of immunization was great. The peripheral blood mononuclear Foxp3mRNA of the patients with pityriasis rose decreased, suggesting that the expression of Treg cells may be reduced and its immunosuppressive function decreased. The transcription factor T-bet, GATA-3, and Foxp3 were all involved in the pathogenesis of pityriasis rosea.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R758.64

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