窄谱中波紫外线对特应性皮炎患者外周血血清胸腺基质淋巴细胞生成素、白细胞介素25及其受体的影响

Effects of narrow-band ultraviolet B on the expressions of thymic stromal lymphopoietin, interleukin-25 and their receptors in peripheral blood of patients with atopic dermatitis

目的：探讨窄谱中波紫外线（NB-UVB）对特应性皮炎（AD）患者血清胸腺基质淋巴细胞生成素（TSLP）、白细胞介素25（IL-25）及外周血单一核细胞（PBMC）TSLP 受体（TSLPR）mRNA、IL-25受体（IL-25R） mRNA 表达水平的影响。方法 AD 患者40例，采用 NB-UVB 照射治疗，双抗体夹心酶联免疫吸附试验（ELISA）检测治疗前后血清中 TSLP、IL-25水平；反转录-聚合酶链反应（RT-PCR）法检测治疗前后 PBMC TSLPR mRNA、IL-25R mRNA 的表达水平。采用欧洲的 AD 评分标准（SCORAD）评估疾病严重程度，视觉模拟标尺法（VAS）评价瘙痒程度。选取30例健康体检者作为对照。组间比较采用两独立样本 t 检验，治疗前后比较采用配对 t 检验。结果患者组经 NB-UVB 照射后总有效率达75%（30/40），治疗后 SCORAD 评分（20.36±5.12）及 VAS 评分（3.05±1.02）均较治疗前（分别为55.26±10.88和8.20±1.37）明显降低，差异均有统计学意义（t 值分别为10.29和8.16，P 〈0.05）。AD 患者组治疗前血清 TSLP [（198.24±29.47）ng/L]、IL-25含量（160.54±34.89 ng/L）及 TSLPR mRNA（8.57±1.34）、IL-25R mRNA（6.81±0.50）相对表达量均明显高于健康对照组[分别为（120.13±19.65）ng/L、（120.41±43.07）ng/L、1.94±0.39、1.48±0.47]，差异均有统计学意义（t 值分别为29.70、14.65、7.07、18.89，P 〈0.05）。NB-UVB 治疗显著改善病情后，患者血清 TSLP[（151.87±14.78） ng/L]、IL-25含量[（130.52±29.65）ng/L]及 PBMC TSLPR mRNA（2.89±0.53）、IL-25R mRNA（3.90±0.37）相对表达量较治疗前明显降低，差异均有统计学意义（t 值分别为18.56、9.07、5.21、7.35，均 P 〈0.05）。治疗后血清TSLP、IL-25含量，PBMC TSLPR mRNA、IL-25R mRNA 相对表达量与健康对照组相比，差异均无统计学意义（P 〉0.05）。结论 TSLP、IL-25可能在 AD 的发病中起重要作用，NB-UVB 下调 TSLP、IL-25及其受体的表达可能是 NB-UVB 治疗 AD 的机制之一。

Objective To explore the effects of narrow-band ultraviolet B （NB-UVB）on the serum levels of thymic stromal lymphopoietin （TSLP）and interleukin-25 （IL-25）, as well as on the expressions of TSLP receptor （TSLPR）and IL-25 receptor （IL-25R）mRNAs in peripheral blood mononuclear cells （PBMCs）from patients with atopic dermatitis（AD）. Methods A total of 40 patients with AD and 30 healthy volunteers were enrolled in this study. All the patients were treated with NB-UVB at 0.3 - 2.5 J/cm2 thrice a week for 12 consecutive weeks. Venous blood samples were obtained from these patients before and after the treatment as well as from these healthy controls. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA）was performed to detect serum levels of TSLP and IL-25, and reverse transcription PCR（RT-PCR）to determine the mRNA expression levels of TSLPR and IL-25R in PBMCs from these subjects. The scoring atopic dermatitis （SCORAD）system developed by the European Task Force on Atopic Dermatitis was used to estimate the severity of AD, and visual analogue scale （VAS）to evaluate the degree of itch. Statistical analysis was carried out by the two-independent-sample t-test for intergroup comparisons and paired t-test for comparisons between pre- and post-treatment samples from these patients. Results After the treatment with NB-UVB, the total response rate reached 75%（30/40）in these patients, with a significant decrease in SCORAD score from 55.26 ± 10.88 before the treatment to 20.36 ± 5.12 after the treatment （t = 10.29, P 〈 0.05）and in VAS score from 8.20 ± 1.37 to 3.05 ± 1.02（t = 8.16, P 〈 0.05）. Before the treatment, the patients showed a significant increase in the serum levels ofnbsp;TSLP（198.24 ± 29.47 ng/L vs. 120.13 ± 19.65 ng/L, t = 29.70, P 〈 0.05）and IL-25（160.54 ± 34.89 ng/L vs. 120.41 ± 43.07 ng/L, t = 14.65, P 〈 0.05）, as well as in the mRNA expression levels of TSLPR （8.57 ± 1.34 vs. 1.94 ± 0.39, t =7.07, P 〈 0.05）and IL-25R（6.81 ± 0.50 vs. 1.48 ± 0.47, t = 18.89, P 〈 0.05）compared with the healthy controls. With the improvement of conditions after the treatment, a significant decrease was observed in the serum levels of TSLP （151.87 ± 14.78 ng/L, t = 18.56, P 〈 0.05）and IL-25（130.52 ± 29.65 ng/L, t = 9.07, P 〈 0.05）, as well as in the mRNA expression levels of TSLPR （2.89 ± 0.53, t = 5.21, P 〈 0.05）and IL-25R （3.90 ± 0.37, t = 7.35, P 〈 0.05）in PBMCs from these patients compared with those before the treatment, and differences disappeared in all of these parameters between the patients and controls （all P 〉 0.05）. Conclusions TSLP and IL-25 may play important roles in the development of AD, and NB-UVB may treat AD by downregulating the expressions of them and their receptors.