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目的探讨DNA甲基转移酶(DNMT)的表达异常在SLE发病中的作用。方法以半定量RT-PCR方法检测了SLE缓解期、活动期及正常人外周血单核细胞(PBMC)中DNMT及CD11a基因表达水平,并进行相关性分析。结果SLE缓解期患者PBMC中DNMT1的表达水平显著低于正常人对照组(t=5.90,P<0.0001);活动期的表达水平也显著低于对照组(t=2.26,P=0.0001);缓解期与活动期比较差异无统计学意义(t=1.75,P=0.089)。SLE缓解期、活动期及对照组PBMC中DNMT3A的表达水平差异无统计学意义,DNMT3B的表达水平极低。SLE缓解期PBMC中CD11a表达水平明显高于对照组(t=5.35,P<0.0001);活动期的表达水平显著高于缓解期(t=2.99,P=0.006)和正常人对照组(t=6.57,P<0.0001)。DNMT1的降低与SLE疾病活动指数(SLEDAI)间无显著相关性(r=-0.34,P>0.05),CD11a的升高与SLEDAI间呈显著正相关(r=0.48,P<0.05),DNMT1与CD11a间无显著相关性(r=-0.18,P>0.05)。结论DNMT1表达水平降低在SLE的发病中可能起作用。但不是决定DNA甲基化状态的惟一因素。
Objective To investigate the role of abnormal expression of DNA methyltransferase (DNMT) in the pathogenesis of SLE. Methods The expression levels of DNMT and CD11a in peripheral blood mononuclear cells (PBMCs) of SLE during remission and active phase were detected by semi-quantitative RT-PCR, and their correlations were analyzed. Results The expression level of DNMT1 in PBMC of patients with SLE was significantly lower than that of normal controls (t = 5.90, P <0.0001), and the activity of DNMT1 was significantly lower than that of controls (t = 2.26, P = 0.0001) There was no significant difference between period and active stage (t = 1.75, P = 0.089). There was no significant difference in the expression level of DNMT3A in PBMC between SLE and active phase and control group, and the expression level of DNMT3B was very low. The expression level of CD11a in PBMC in SLE group was significantly higher than that in control group (t = 5.35, P <0.0001), and the expression level in active stage was significantly higher than that in remission group (t = 2.99, 6.57, P <0.0001). There was no significant correlation between the decrease of DNMT1 and SLEDAI (r = -0.34, P> 0.05). The increase of CD11a was positively correlated with SLEDAI (r = 0.48, P <0.05) There was no significant correlation between CD11a (r = -0.18, P> 0.05). Conclusions Decreased DNMT1 expression may play a role in the pathogenesis of SLE. But not the only factor that determines DNA methylation status.