窄谱中波紫外线照射对特应性皮炎小鼠皮损中丝聚蛋白和胸腺基质淋巴生成素表达的影响及可能机制

Influences of NB-UVB irradiation on the expressions of filaggrin and thymic stromal lymphopoietin in atopic dermatitis mice and its potential mechanism

目的检测窄谱中波紫外线(narrow-band ultraviolet B,NB-UVB)照射对特应性皮炎(atopic dermatitis,AD)小鼠皮损中丝聚蛋白(filaggrin,FLG)和胸腺基质淋巴生成素(thymic stromal lymphopoietin,TSLP)表达的影响,探讨其治疗AD的可能机制。方法16只C57BL/6J小鼠分为照光组和非照光组,每组8只,于实验第1~9天,每日将钙泊三醇(2 nmol/L)局部外用于2组小鼠背部制备AD小鼠模型,模型制备同时照光组采用NB-UVB照射,隔日1次。观察2组小鼠皮损临床表现及第2、4、6、8天皮损严重程度评分和病理学表现;采用实时荧光定量PCR法检测AD小鼠皮损中FLG、TSLP mRNA相对表达量及AD小鼠皮损引流淋巴结中白细胞介素(interleukin,IL)-4、IL-13、协同刺激分子配体(OX40-ligand,OX40L)、TSLP受体(thymic stromal lymphopoietin receptor,TSLPR)mRNA相对表达量。结果照光组小鼠第2、4、6、8天皮损严重程度评分[(0.670±0.516)、(1.330±0.516)、(1.670±0.516)、(2.170±0.408)分]均低于非照光组[(1.500±0.548)、(2.160±0.408)、(2.500±0.548)、(2.830±0.408)分](P<0.05),且皮损组织海绵水肿、淋巴细胞浸润等炎症表现较非照光组轻。照光组皮损组织TSLP mRNA相对表达量(0.417±0.040)低于非照光组(1.000±0.092)(P<0.05),FLG mRNA相对表达量(1.860±1.187)高于非照光组(1.000±0.523)(P<0.05);照光组皮损引流淋巴结中IL-13 mRNA(0.528±0.160)、OX40L mRNA(0.634±0.178)及TSLPR mRNA(0.669±0.075)相对表达量均低于非照光组(1.000±0.404、1.000±0.312、1.000±0.241)(P<0.05),IL-4 mRNA相对表达量(0.909±0.180)与非照光组(1.000±0.205)比较差异无统计学意义(P>0.05)。结论NB-UVB照射可能通过上调AD小鼠皮损中屏障蛋白FLG表达,下调TSLP表达,并降低IL-13、OX40L及TSLPR等相关炎性因子表达,从而发挥治疗AD的作用。

Objective To investigate the influences of narrow-band ultraviolet B(NB-UVB)irradiation on the expressions of filaggrin(FLG)and thymic stromal lymphopoietin(TSLP)in atopic dermatitis(AD)mice and the potential mechanism.Methods Sixteen C57 BL/6 J mice were equally divided into irradiation group and non-irradiation group.Calcipotriol(2 nmol/L)was applied topically on the backs of the mice in two groups on the 1 st to 9 th days of experiment to prepare AD mice models.NB-UVB irradiation was used once every other day in irradiation group.The clinical and pathological manifestations of skin lesions were observed and the severity scores on day 2,4,6 and 8 were recorded in two groups.Real-time fluorescence quantitative PCR was used to detect the mRNA expression of FLG and TSLP in skin lesions,as well as the mRNA expressions of interleukin(IL)-4,IL-13,OX40-ligand(OX40 L)and TSLP receptor(TSLPR)in the draining lymph nodes of AD mice.Results After NB-UVB irradiation,the severity scores on day 2,4,6 and 8 were lower in irradiation group(0.670±0.516,1.330±0.516,1.670±0.516,2.170±0.408)than those in non-irradiation group(1.500±0.548,2.160±0.408,2.500±0.548,2.830±0.408)(P<0.05).The inflammatory manifestations such as sponge edema and lymphocyte infiltration in skin lesions were milder in irradiation group than those in non-irradiation group.The relative expression of TSLP mRNA was lower in irradiation group(0.417±0.040)than that in non-irradiation group(1.000±0.092)(P<0.05),while the relative expression of FLG mRNA was higher in irradiation group(1.860±1.187)than that in non-irradiation group(1.000±0.523)(P<0.05).The relative expressions of IL-13 mRNA(0.528±0.160),OX40 L mRNA(0.634±0.178)and TSLPR mRNA(0.669±0.075)in the drainage lymph nodes in irradiation group were lower than those in non-irradiation group(1.000±0.404,1.000±0.312,1.000±0.241)(P<0.05),while the relative expression of IL-4 mRNA showed no significant difference between irradiation group(0.909±0.180)and non-irradiation group(1.000±0.205)(P>0.05).Conclusion NB-UVB irradiation may play a therapeutic role by up-regulating the expression of FLG and down-regulating the expression of TSLP in skin lesions of AD mice,as well as reducing the expressions of IL-13,OX40 L,TSLPR and other relevant inflammatory cytokines.