甲氨蝶呤对寻常性银屑病患者外周血CD14~+单核细胞Toll样受体2,4表达的影响

摘要

目的 探讨Toll样受体(TLR)2、TLR4在寻常性银屑病发病巾的作用及甲氨蝶呤对其表达的影响,探讨甲氨蝶呤治疗寻常性银屑病的机制.方法 采用流式细胞术检测43例寻常性银屑病患者治疗前、甲氨蝶呤治疗4周后、8周后外周血CD14~+单核细胞TLR2、TLR4的表达情况,以30例正常人作为对照组.结果 治疗前寻静性银屑病患者外周血中CD14~+单核细胞TLR2表达率为(92.6±4.3)%,TLR4表达率为(48.5±4.6)%,均较正常人对照组明显增高(P值均＜0.01).进行期寻常性银屑病患者TLR2、TLR4的表达率分别为(97.5±4.1)%、(55.3±5.8)%,静止期患者分别为(87.6±5.6)%、(40.7±7.1)%,两组之间TLR2、TLR表达率差异均有统计学意义(P值均＜0.05).经甲氨蝶呤治疗后TLR2、TLR4的表达率分别为(79.6±6.7)%、(34.6±5.9)%,明显低于治疗前(P值均＜0.05).TLR2和TLR4表达率与银屑病PASI评分无明显相关性(r值分别为0.24,0.27,P值均＞0.05).结论 TLR2、TLR4及其介导的天然免疫应答在银屑病发病机制中可能起重要作用,而甲氨蝶呤可能通过抑制TLR2、TLR4表达而发挥作用.%Objective To investigate the expressions of TLR2 and TLR4 in patients with psoriasis vulgaris and the efrect of methotrexate(MTX)on them.so as to explore the therapeutic mechanism of MTX in psoriasis vulgafis.Methods Forty-three patients with psoriasis vulgaris were recruited into the study together with 30 normal human controls.Oral MTX was given to patients with an interval of 12 hours for three times per week until the control of conditions followed by 4 weeks of mainmining treatment.The dosage of MTX was 5 mg initially and decreased to 2.5 mg in the maintaining period.Flow cytometry was used to detect the expression of TLR2 and TLR4 in peripheral blood CD14~+ cells from the controls and patients at baseline,4 and 8 weeks after the beginning of treatment.Results The expression rate of TLR2 and TLR4 in CD14~+ cells was(92.6±4.3)%and(48.5±4.6)%,respectively,in untreated patients,significantly higher than that in normal controls(botll P＜0.01).A significant increase was observed in the expression rate of TLR2 and TLR4 in patients with active psoriasis compared with those with inactive psoriasis [(97.5±4.1)%vs(87.6±5.6)%,(55.3±5.8)%vs(40.7±7.1)%,both P＜0.05].Eigh weeks after the beginning of treatment with MTX.the expression rate of TLR2 and TLR4 significantly decreased to (79.6±6.7)%and(34.6±5.9)%.respectively(both P＜0.05).The psoriasis area and severity index(PASI)score had no significant correlation with the expression rate of TLR2 or TLR4(r=0.24.0.27,both P＞0.05).Conclusions TLR2,TLR4 and innate immune response mediated by both receptors play an important role in the pathogenesis of psoriasis.MTX may exert its therapeutic effect on psoriasis by inhibiting the expression of TLR2 and TLR4.