本文選題：系統(tǒng)性紅斑狼瘡 + 5-羥甲基化胞嘧啶��； 參考：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]通過檢測系統(tǒng)性紅斑狼瘡(systemiclupuserythematosus,SLE)患者和正常對照外周血單個(gè)核細(xì)胞DNA羥甲基化的水平,分析DNA羥甲基化與SLE的關(guān)系;同時(shí)探索SLE患者的羥甲基化與合并癥及臨床表型之間的關(guān)系。[方法]本研究首次采用ELISA法檢測95例SLE患者及77例正常健康對照者外周單個(gè)核細(xì)胞DNA5-羥甲基胞嘧啶(5-hydroxymethylcytosine,5-hmC)的水平,比較兩者之間的差異,分析DNA羥甲基化水平與SLE的關(guān)系。同時(shí)收集患者相關(guān)實(shí)驗(yàn)室檢查,對SLE患者5-hmC的水平與系統(tǒng)性紅斑狼瘡患者合并癥及臨床表型之間的相關(guān)性進(jìn)行統(tǒng)計(jì)、比較,從而了解5-hmC含量的改變與系統(tǒng)性紅斑狼瘡相關(guān)的合并癥及臨床表型的關(guān)系。[結(jié)果](1)本研究共納入SLE患者95例,其中男性17例,女性78例,年齡在16-60歲,平均年齡35.38± 14.39歲;對照組為77例,其中男性為16例,女性61例,年齡在16-60歲,平均年齡在37.22 士 13.92歲�；颊呓M和正常對照組之間性別、年齡均無明顯統(tǒng)計(jì)學(xué)差異(P0.05)。(2)SLE 患者 5-hmC 平均含量為 0.063±0.0029%,對照組為 0.069±0.0032%,SLE患者羥甲基水平下降約0.006%,差異有顯著統(tǒng)計(jì)學(xué)差異(t=12.468,P0.001)。進(jìn)一步分析發(fā)現(xiàn),SLE患者5-hmC的含量與SLEDAI評分呈負(fù)相關(guān)關(guān)系(r=-0.317,P =0.004)。(3)SLE患者的5-hmC水平分別與總膽紅素(r=0.223,P=0.033)、直接膽紅素(r=0.213,P=0.043)、間接膽紅素(r=0.247,P=0.018)及 k 鏈(r=0.399,P=0.011)正相關(guān),進(jìn)一步分析發(fā)現(xiàn),SLEDAI評分分別與總膽紅素(r =-0.311,P=0.005)、直接膽紅素(r=-0.244,P=0.030)、間接膽紅素(r =-0.290,P=0.009)呈負(fù)相關(guān);SLE患者的5-hmC水平分別與尿微量白蛋白(r=-0.330,P =0.007)及尿白蛋白肌酐比值(r=-0.265,P=0.031)負(fù)相關(guān)。但相關(guān)系數(shù)r絕對值在0.2-0.4之間,相關(guān)性為低度相關(guān),結(jié)果有待進(jìn)一步擴(kuò)大樣本驗(yàn)證。(4)無腎炎SLE患者5-hmC含量高于SLE合并腎炎(SLE+LN)患者5-hmC含量(0.062 vs0.064,P=0.027);SLE患者5-hmC含量高于SLE+高血壓患者5-hmC含量(0.062vs0.064,P=0.021);而SLE繼發(fā)干燥綜合征、抗磷脂綜合征、NPSLE、血液系統(tǒng)受累、甲狀腺疾病、感染等合并癥時(shí),5-hmC含量變化不明顯(P0.05)。(5)核小體抗體陰性SLE患者5-hmC含量高于核小體抗體陽性患者(P=0.043),差異有統(tǒng)計(jì)學(xué)意義,而與所檢測的ANA滴度、ANA核型、ds-DNA抗體、抗組蛋白抗體、Sm抗體、U1snRNP抗體、SSA-RO60KD抗體、SSA-R052KD抗體、SSB抗體、抗核糖體抗體之間不存在統(tǒng)計(jì)學(xué)差異。[結(jié)論](1)SLE外周血DNA5-hmC可能存在改變,可能參與了 SLE的發(fā)病。(2)SLE患者外周血5-hmC的含量與SLE疾病嚴(yán)重程度呈負(fù)相關(guān),或可作為SLE活動度的標(biāo)志物。(3)5-hmC含量降低與狼瘡性腎炎的發(fā)生相關(guān),因此檢測5-hmC含量或可有利于早期發(fā)現(xiàn)狼瘡性腎炎。(4)5-hmC可能影響某些自身抗體的產(chǎn)生(尤其是核小體抗體),參與自身免疫過程。
[Abstract]:[objective] to analyze the relationship between DNA hydroxymethylation and SLE in peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) and normal controls. At the same time, to explore the relationship between hydroxymethylation and complications and clinical phenotypes in patients with SLE. [methods] the peripheral mononuclear cells DNA5-hydroxymethylcytosine 5-HmC- (5-HMC) levels in 95 patients with SLE and 77 healthy controls were detected by ELISA method for the first time, and the relationship between DNA hydroxymethylation and SLE was analyzed. At the same time, the correlation between the 5-hmC level of SLE patients and the complications and clinical phenotypes of patients with systemic lupus erythematosus was analyzed and compared. To understand the relationship between the changes of 5-hmC content and systemic lupus erythematosus associated complications and clinical phenotypes. [results] A total of 95 patients with SLE were included in this study, including 17 males and 78 females, with an average age of 35.38 鹵14.39 years, and 77 patients in the control group (16 males and 61 females, aged 16-60 years). The average age was 37.22 鹵13.92 years old. There was no significant difference in sex and age between the patient group and the normal control group. The average content of 5-hmC in the patients with SLE was 0.063 鹵0.0029, while that in the control group was 0.069 鹵0.0032. The level of hydroxymethyl decreased by 0.006. There was a significant difference between the two groups. Further analysis showed that there was a negative correlation between the 5-hmC content and the SLEDAI score. The 5-hmC levels were positively correlated with the total bilirubin level 0.223P 0.033, direct bilirubin 0.213P 0.43, indirect bilirubin 0.247P0. 018) and k chain ru 0.399P0. 011), respectively. Further analysis showed that the SLEDAI score was negatively correlated with the total bilirubin r-0.311P0. 005, direct bilirubin r-0.244 P0. 030, indirect bilirubin r-0.290 P0. 009), and the 5-hmC level negatively correlated with the urinary albumin r-0. 330 P0. 007) and the urinary albumin creatinine ratio (r-0. 265 P 0. 031). But the absolute value of correlation coefficient r is between 0.2-0.4, the correlation is low correlation, Results the content of 5-hmC in SLE patients without glomerulonephritis was higher than that in patients with SLE combined with glomerulonephritis. The content of 5-hmC in patients with SLE hypertension was higher than that in patients with SLE hypertension, while that in patients with SLE secondary to Sjogren's syndrome was higher than that in patients with SLE hypertension. In patients with antiphospholipid syndrome, blood system involvement, thyroid disease, infection and other complications, the level of 5-hmC in patients with negative nucleosome antibody was higher than that in patients with positive nucleosome antibody (P 0.043), and there was no significant change in the content of 5-HMC in patients with complicated diseases such as thyroid disease and infection. However, there was no statistical difference between the ANA titer and the detected ANA karyotypes, such as anti-histone antibody, U1snRNP antibody, SSA-RO60KD antibody, SSA-R052KD antibody, and anti-ribosomal antibody. [conclusion] there may be changes in peripheral blood DNA5-hmC in patients with SLE, which may be involved in the negative correlation between the 5-hmC content in peripheral blood and the severity of SLE disease, or as a marker of SLE activity. The decrease of 5-HMC level may be associated with the occurrence of lupus nephritis. Therefore, the detection of 5-hmC may be helpful to the early detection of lupus nephritis. 45-HMC may affect the production of some autoantibodies (especially nucleosome antibody), and participate in the autoimmune process.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R593.241

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