本文選題：強直性脊柱炎 + miR-155��； 參考：《安徽醫(yī)科大學(xué)》2015年碩士論文

【摘要】：背景微小RNA(mic RNA)是一類染色體上高度保守的非編碼單鏈RNA,廣泛存在于真核生物中,它通過與靶基因特異性結(jié)合,引起靶基因m RNA的降解或干擾蛋白質(zhì)的翻譯過程,并可在特定條件下上調(diào)靶基因的蛋白表達(dá)和信使RNA的水平。mi RNA參與了生物體多種生理和病理過程,并在固有免疫、適應(yīng)性免疫及炎癥因子的信號轉(zhuǎn)導(dǎo)過程中發(fā)揮著關(guān)鍵性的調(diào)節(jié)作用。強直性脊柱炎(ankylosing spondylitis,AS)是一種類風(fēng)濕因子陰性的慢性炎癥性自身免疫性疾病,以侵犯中軸骨骼為主,時常累及外周關(guān)節(jié)、肌腱韌帶附著點及其它軟骨組織,引起脊柱強直和纖維化。AS的病因及發(fā)病機制至今仍不明確,可能與遺傳、免疫、慢性感染、遺傳與環(huán)境的交互作用等有關(guān)。細(xì)胞因子在免疫細(xì)胞的生長、分化及免疫調(diào)節(jié)中發(fā)揮信號傳遞作用。本課題組前期發(fā)現(xiàn)了多種細(xì)胞因子,如IL-6、IL-12、IL-17在AS中的異常表達(dá),本研究擬通過檢測AS患者部分mi RNA的表達(dá)水平并探討與以上細(xì)胞因子的相關(guān)性,為強直性脊柱炎病因及治療提供線索和依據(jù)。目的通過檢測AS患者外周單個核細(xì)胞中mi R-155、mi R-16、mi R-31、mi R-181a表達(dá)水平,并分析mi R-155、mi R-16、mi R-31、mi R-181a與血清細(xì)胞因子、臨床指標(biāo)、疾病活動度的相關(guān)性,探討mi R-155、mi R-16、mi R-31、mi R-181a在AS發(fā)生和發(fā)展中所起到的作用及意義。方法采用熒光定量PCR檢測40名AS患者和40名健康對照組外周單個核細(xì)胞中mi R-155、mi R-16、mi R-31、mi R-181a表達(dá)水平。AS患者來源于安徽醫(yī)科大學(xué)第一附屬醫(yī)院風(fēng)濕免疫科,根據(jù)強直性脊柱炎活動指數(shù)將AS患者分為活動組和穩(wěn)定組;選取同期合肥市中心血站健康獻(xiàn)血者作為對照組。采用酶聯(lián)免疫吸附法(ELISA),檢測AS患者細(xì)胞因子IL-6、IL-12、IL-17、IL-10,TNF-a和健康對照血清TNF-a,IL-10的水平,分析AS組與健康對照組間TNF-a,IL-10的水平。進一步分析病例組mi R-155、mi R-16、mi R-31、mi R-181a表達(dá)水平與細(xì)胞因子、疾病活動度、ESR、CRP等臨床指標(biāo)的相關(guān)性。結(jié)果本研究發(fā)現(xiàn)AS患者外周單個核細(xì)胞中mi R-31的表達(dá)顯著高于健康對照組(Z=-4.007,p0.001),而mi R-155,mi R-16,mi R-181a外周血單個核細(xì)胞表達(dá)在強直性脊柱炎和健康對照組之間無統(tǒng)計學(xué)差異(Z=-1.095,P=0.274;Z=-1.555,P=0.120;Z=-1.720,P=0.086)。病情穩(wěn)定組與活動組中mi R-155,mi R-16,mi R-181a,mir-31的表達(dá)無差異(Z=-0.525,P=0.607;Z=-0.818,P=0.421;Z=-0.812,P=0.434;Z=-0.66,P=0.517)。同時,mi R-155,mi R-16,mi R-181a,mi R-31的表達(dá)與各細(xì)胞因子IL-6、IL-12、IL-17、IL-10,TNF-a均無相關(guān)性(P均0.05)。mi R-155,mi R-16,mi R-181a,mi R-31的表達(dá)與疾病活動指數(shù)、ESR、CRP之間均無相關(guān)性(p均0.05)。但I(xiàn)L-6、IL-12與疾病活動指數(shù)具有相關(guān)性(p0.05)。結(jié)論AS患者外周血單個核細(xì)胞中mi R-31表達(dá)上調(diào),提示可能在AS的發(fā)病中起到重要的作用。
[Abstract]:Background microRNAs are a class of highly conserved non-coding single-stranded RNAs on chromosomes, which are widely found in eukaryotes. By specifically binding with target genes, mic RNAs cause the degradation of target genes and interfere with the process of protein translation. And can up-regulate the protein expression of target gene and the level of messenger RNA under certain conditions. Mi RNA is involved in many physiological and pathological processes of organism and innate immunity. Adaptive immunity and the signal transduction of inflammatory factors play a key role in regulation. Ankylosing spondylitis as (as) is a chronic inflammatory autoimmune disease with negative rheumatoid factor. The etiology and pathogenesis of spinal ankylosis and fibrosis as are still unclear, which may be related to heredity, immunity, chronic infection, interaction between heredity and environment, etc. Cytokines play a signalling role in the growth, differentiation and immunomodulation of immune cells. Several cytokines, such as the abnormal expression of IL-6, IL-12, IL-17, were found in the early stage of the study. This study was intended to detect the expression level of partial mi RNA in patients with as and to explore the correlation with the above cytokines. To provide clues and evidence for the etiology and treatment of ankylosing spondylitis. Objective to detect the expression level of mi R-155n mi R-16tmmi R-31a in peripheral mononuclear cells (PBMC) of as patients, and to analyze the correlation between the expression of mi R-155Mi R-16mmi R-31mmiR-181a and serum cytokines, clinical indexes and disease activity. This paper discusses the role and significance of mi R-155U mi R-16C mi R-31M R-181a in the occurrence and development of as. Methods fluorescence quantitative PCR was used to detect the expression of mi R-155N mi R-16M R-31mmi R-181a in peripheral mononuclear cells of 40 patients with as and 40 healthy controls. The patients with as were from the Department of Rheumatology and Immunology of the first affiliated Hospital of Anhui Medical University. According to the activity index of ankylosing spondylitis, patients with as were divided into active group and stable group. Enzyme linked immunosorbent assay (Elisa) was used to detect the levels of the cytokine IL-6, IL-12, IL-17, IL-10, and the serum levels of TNF-a, IL-10 in healthy controls, and the levels of TNF-a IL-10 between as group and healthy control group were analyzed by enzyme-linked immunosorbent assay (Elisa). Further analysis was made on the correlation between the expression of miR-155nmi R-16mR-31mil R-181a and cytokines, disease activity and ESR-CRP, and so on. Results the expression of miR-31 in peripheral mononuclear cells in patients with as was significantly higher than that in healthy controls (ZF-4.007p0.001), while the expression of MIR-155mR-16mR-181a in peripheral blood mononuclear cells was not significantly different between the patients with ankylosing spondylitis and the healthy controls (Z-1.095P0.274Z-1.555P0. 120-1.720P0.086). The expression of miR-31 in peripheral mononuclear cells in patients with as was significantly higher than that in healthy controls (Z-4.007p0.001), but there was no significant difference in the expression of MIR-181a between ankylosing spondylitis and healthy controls. There was no difference in the expression of mi R-155nmi R-16nmi R-181a mir-31 between the stable group and the active group (ZAM-0.525, P ~ 0.607, P ~ (0.607), P ~ (0.421), P ~ (0.421), P ~ (0.434), P ~ (0.434), Z ~ (-0.66), P _ (0.517). At the same time, there was no correlation between the expression of R-155Mi R-181ammi R-31 and the cytokines IL-6, IL-12, IL-17, IL-10, TNF-a (P 0.05) .mi R-155mi R-165mi R-181a mi R-31 and disease activity index (ESRCRP) (p < 0.05). But IL-6 and IL-12 were correlated with disease activity index (p0.05). Conclusion the expression of miR-31 in peripheral blood mononuclear cells is up-regulated in patients with as, suggesting that it may play an important role in the pathogenesis of as.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R593.23

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相關(guān)期刊論文 前1條

1 范薇;沈南;唐元家;;MicroRNA參與系統(tǒng)性紅斑狼瘡發(fā)病機制的研究進展[J];現(xiàn)代免疫學(xué);2010年04期

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本文編號：2057440