雌激素、肼苯哒嗪和紫外线对SLE患者甲基转移酶活性的影响

Effect of estrogen, hydralazine and ultraviolet ray on DNA methyltransferase-1 activity in patients with systemic lupus erythematosus

目的 探讨雌激素、肼苯哒嗪、紫外线（UVB）照射诱导SLE发病的作用机制.方法 分离、培养10例SLE患者和9例正常人外周血单核细胞（PBMC）,分别进行雌激素、肼苯哒嗪和UVB照射等干预.采用甲基转移酶（DNMT）激活/抑制法检测PBMC的DNMT1活性.结果 SLE患者DNMT1活性（0.36±0.24）较正常人对照（0.46±0.17）差异无统计学意义（P＞0.05）,雌激素干预后SLE患者DNMT1活性显著低于正常人对照（0.32±0.18比0.46±0.17,t=1.725,P＜0.05）,肼苯达嗪干预后SLE患者DNMT1活性显著低于正常人对照（0.33±0.13比0.46±0.17,t=1.739,P＜0.05）,UVB干预后SLE患者DNMT1活性显著低于正常人对照（0.30±0.14比0.46±0.17,t=1.739,P＜0.05）.另外,肼苯达嗪干预的正常人DNMT1活性（0.38±0.12）也显著低于正常人（0.46±0.17）对照（P＜0.05）.结论 雌激素、肼苯哒嗪和UVB照射等因素具有抑制SLE患者DNMT1活性的作用,提示三个诱发因素可能通过改变DNMT活性来诱导SLE发病.

Objective To explore the mechanism underlying the induction of systemic lupus erythematosus （SLE） by estrogen, hydralazine and ultraviolet irradiation. Methods Peripheral blood mononuclear cells （PBMCs） were harvested from 10 patients with SLE and 9 normal human controls, and cultured with or without the intervention with estrogen, hydralazine or ultraviolet irradiation. The DNA methyltransferase-1 （DNMT1） activity of PBMCs was quantified by using DNMT activity/inhibition assay kit. Results No statistical difference was observed in DNMT1 activity between patients with SLE and normal controls （0.36 ± 0.24 vs 0.46 ± 0.17, P ＞ 0.05）. A significant decrease was noted in DNMT1 activity in PBMCs from patients with SLE after intervention with estrogen （0.32 ± 0.18 vs 0.46 ± 0.17, t = 1.725, P ＜ 0.05）, hydralazine （0.33 ±0.13 vs 0.46 ± 0.17, t = 1.739, P ＜ 0.05） and ultraviolet irradiation （0.30 ± 0.14 vs 0.46 ± 0.17, t = 1.739,P ＜ 0.05 ） compared with that from normal human controls. The treatment with hydralazine also induced an attenuation of DNMT1 activity in PBMCs from normal human controls （0.38 ± 0.12 vs 0.46 ± 0.17, P＜ 0.05）.Conclusion Estrogen, hydralazine and ultraviolet irradiation can inhibit the DNMT1 activity of SLE patients,indicating that they may induce the initiation of SLE by altering the activity of DNMT1.