【摘要】 目的:探讨三氧化二砷(arsenic trioxide,ATO)及5-氮胞苷(5-Aza)对MRL/lpr狼疮小鼠免疫状况和基因甲基化的影响。方法:12周龄MRL/lpr小鼠36只,随机分为3组分别给ATO、5-Aza与生理盐水(NS),疗程为60d。分别检测治疗前后抗dsDNA抗体,治疗后用高效液相方法检测脾脏、淋巴结、胸腺和血液DNA甲基化水平。结果:(1)治疗后ATO组血清抗dsDNA抗体明显低于NS组与5-Aza组(P<0.01);(2)治疗后ATO组脾脏及淋巴结重量较NS组与5-Aza组有明显减轻(P<0.05);(3)治疗后ATO组脾脏及淋巴结的甲基化水平较NS组有明显升高(P<0.05),而血液及胸腺甲基化水平两组间差异无统计学意义,治疗后5-Aza组脾脏、淋巴结及血液的甲基化水平较NS组明显下降(P<0.05)。结论:ATO能够降低小鼠外周血抗dsDNA抗体水平并抑制淋巴组织的增生,明显提高脾脏和淋巴结的基因甲基化水平。更多还原

【Abstract】 Objective:To investigate the effect of arsenic trioxide and 5-Aza on the immune status and DNA methylation in MRL/lpr mice.Methods:Thirty six 12-week-old MRL/lpr mice were randomly divided into three groups including arsenic trioxide group,5-azacytidine group and normal saline group.The treatment was conducted for two months.The level of anti-dsDNA antibodies was measured before treatment.After the treatment,the level of anti-dsDNA antibodies,organs weights and the levels of DNA methylation in spleen,thymus,blood and lymphaden were measured.Results:(1)After treatment,the level of anti-dsDNA antibodies in ATO group was significantly lower than that in NS and 5-azacytidine group (P<0.01).(2)After treatment,the weights of spleen and lymphaden in ATO group were lower than those in NS group and 5-azacytidine group (P<0.05).(3)The levels of methylation of spleens and lymphadens in ATO group were significantly higher than those in NS group(P<0.05).But there were no significanct difference in the levels of methylation of blood and thymus in the three groups.Conclusion:Arsenic trioxide can inhibit the production of anti-dsDNA antibody and suppress the hyperplasia of immune organ, and elevate the DNA methylation in spleen and lymphaden of MRL/lpr mice.更多还原