本文選題：系統(tǒng)性紅斑狼瘡 + 白介素-23��； 參考：《吉林大學(xué)》2015年博士論文

【摘要】：系統(tǒng)性紅斑狼瘡（Systemic Lupus Erythematosus，SLE）是自身免疫介導(dǎo)的、以免疫性炎癥為突出表現(xiàn)的彌漫性結(jié)締組織病。狼瘡腎炎（Lupus Nephritis，LN）是SLE最嚴(yán)重的并發(fā)癥之一，也是SLE患者最主要的死因之一，早期診斷和規(guī)范的治療是提高LN預(yù)后的關(guān)鍵所在，但由于缺少對SLE及LN的發(fā)病機(jī)制的深入了解，所以目前對SLE以及LN的治療仍為控制病情進(jìn)展，因此對SLE以及LN具體的致病機(jī)制的探討迫在眉睫。已有研究證實(shí)輔助性T細(xì)胞17（Th17cell）通過分泌白介素-17（IL-17）等細(xì)胞因子在SLE及LN的發(fā)生發(fā)展中發(fā)揮非常重要的作用，而Th17細(xì)胞的增殖與分化受到白介素-23（IL-23）的嚴(yán)格調(diào)控。IL-23是一種異二聚體組成的細(xì)胞因子，多種組織和細(xì)胞均可分泌IL-23, SLE患者體內(nèi)的單核巨噬細(xì)胞可分泌大量的IL-23，IL-23通過與Th17細(xì)胞表面的受體結(jié)合促進(jìn)IL-17的大量分泌，從而使SLE進(jìn)行性加重。 本研究應(yīng)用RT-PCR等技術(shù)檢測了158例SLE患者和60例健康對照組外周血IL-23和IL-17mRNA的水平，并分析了外周血IL-23mRNA和IL-17mRNA/IL-23mRNA比值的變化與SLE發(fā)生發(fā)展的關(guān)系；進(jìn)一步明確SLE患者外周血IL-23mRNA和IL-23與LN的發(fā)病及嚴(yán)重程度有關(guān)系。 結(jié)果顯示，與健康對照組相比，SLE患者的外周血IL-23mRNA表達(dá)水平以及IL-17mRNA/IL-23mRNA的比值均明顯上升，差異有統(tǒng)計(jì)學(xué)意義（P＜0.001）；而且SLE患者的外周血IL-23mRNA表達(dá)水平上升與性別、SLE疾病活動度無關(guān)；與健康對照組相比，LN患者的外周血IL-23mRNA和蛋白表達(dá)水平上調(diào)更加明顯，并且差異有統(tǒng)計(jì)學(xué)意義，（P＜0.001）。對LN患者IL-23mRNA的表達(dá)水平與RenalSLEDAI評分做了相關(guān)性分析，二者呈明顯正相關(guān)（r=0.9210，P0.0001）。與健康對照組及非LN組比較，LN組外周血IL-23的表達(dá)水平明顯升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.001）。 本研究的創(chuàng)新之處在于：第一，本研究首次從分子水平闡明IL-23mRNA表達(dá)水平以及IL-17mRNA/IL-23mRNA的比值與SLE的發(fā)病密切相關(guān)，為SLE發(fā)病機(jī)理的研究提供新的證據(jù)；第二，本研究從分子水平闡明IL-23mRNA水平與SLE的發(fā)病有關(guān)，與SLE的疾病活動性沒有直接關(guān)系；第三，本研究首次證實(shí)，外周血IL-23mRNA水平與LN的關(guān)系更為密切，為LN治療提供新的靶點(diǎn)。 總之，，本研究為SLE發(fā)病機(jī)制的研究提供新的證據(jù)，為LN的治療提供新的靶點(diǎn)。
[Abstract]:Systemic lupus erythematosus (SLE) is an autoimmune mediated diffuse connective tissue disease characterized by immune inflammation. Lupus nephritis (LN) is one of the most serious complications of SLE and one of the most important cause of death in SLE patients. Early diagnosis and standardized treatment are the key to improve the prognosis of LN. However, there is a lack of in-depth understanding of the pathogenesis of SLE and LN. So at present, the treatment of SLE and LN is still to control the progress of the disease, so it is urgent to explore the specific pathogenesis of SLE and LN. It has been proved that T helper cell 17 (Th17cell) plays a very important role in the pathogenesis and development of SLE and LN by secreting cytokines such as interleukin-17 (IL-17). The proliferation and differentiation of Th17 cells are strictly regulated by interleukin-23 (IL-23). IL-23 is a cytokine composed of heterodimer. A variety of tissues and cells can secrete IL-23. Mononuclear macrophages in SLE patients can secrete a large amount of IL-23 and IL-23 can promote the secretion of IL-17 by binding to the receptors on the surface of Th17 cells. In this study, the levels of IL-23 and IL-17 mRNA in peripheral blood of 158 SLE patients and 60 healthy controls were detected by RT-PCR, and the relationship between the ratio of IL-23 mRNA and IL-17mRNA-IL-23 mRNA in peripheral blood and the occurrence and development of SLE was analyzed. To further clarify the relationship between IL-23 mRNA and IL-23 in peripheral blood of SLE patients and the pathogenesis and severity of LN. The results showed that the expression level of IL-23 mRNA and the ratio of IL-17 mRNA-IL-23 mRNA in peripheral blood of SLE patients were significantly higher than those in healthy controls (P < 0.001), and the increase of IL-23 mRNA expression in peripheral blood was not related to the disease activity of SLE patients. The expression of IL-23 mRNA and protein in peripheral blood of LN patients was significantly higher than that of healthy controls (P < 0.001). The expression of IL-23 mRNA was positively correlated with the Renal SLEDAI score in LN patients (r = 0.9210, P 0.0001). The expression of IL-23 in peripheral blood of LN group was significantly higher than that of healthy control group and non-LN group (P < 0.001). The innovations of this study are as follows: firstly, the expression level of IL-23 mRNA and the ratio of IL-17mRNA-IL-23 mRNA to the pathogenesis of SLE were elucidated for the first time in this study, which provided new evidence for the study of pathogenesis of SLE; second, the expression level of IL-23 mRNA and the ratio of IL-17mRNA-IL-23 mRNA were closely related to the pathogenesis of SLE. In this study, the molecular level of IL-23 mRNA was demonstrated to be related to the pathogenesis of SLE, but not to the disease activity of SLE. Third, it was first confirmed that the level of IL-23 mRNA in peripheral blood was more closely related to LN, which provided a new target for the treatment of LN. In conclusion, this study provides new evidence for the pathogenesis of SLE and a new target for the treatment of LN.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R593.241

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;系統(tǒng)性紅斑狼瘡診治指南(草案)[J];中華風(fēng)濕病學(xué)雜志;2003年08期

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