他克莫司对特应性皮炎皮损中蛋白酶活化受体2表达的影响

Effects of tacrolimus on the expression of proteinase activated receptor 2 in lesions of atopic dermatitis

目的 观察蛋白酶活化受体2（PAR-2）在特应性皮炎（AD）患者皮肤中的表达以及他克莫司对其表达的影响.方法 比较6例中重度AD患者外用0.1%他克莫司软膏治疗3周前后的临床症状、体征变化,切取患者治疗前后皮损及外观正常的皮肤,6例正常皮肤作对照,免疫组化方法检测皮肤PAR-2的表达变化.结果 PAR-2在皮肤的表皮全层尤其是颗粒层以及毛囊、汗腺、血管内皮细胞、神经纤维样结构均表达.AD患者皮损内角质形成细胞PAR-2染色的平均吸光度为4339.6±115.8,与非皮损部位（4189.0±228.9）和正常对照皮肤（3864.0±237.3）比较,其表达明显升高（t=2.85,P〈0.05;t=4.31,P〈 0.05）;0.1%他克莫司软膏治疗3周后原皮损处角质形成细胞PAR-2染色的平均吸光度为3942.4±176.6,表达较治疗前明显下降（t=4.55,P〈 0.05）;PAR-2的表达水平与AD患者的瘙痒VAS评分、EASI指数和IGA评分均呈正相关.结论 PAR-2在AD患者皮损角质形成细胞内的表达增加,表达水平与瘙痒程度和皮损严重程度呈正相关,PAR-2在皮损角质形成细胞内的过度表达可被他克莫司抑制.

Objective To detect the expression of proteinase activated receptor 2 （PAR-2） in the skin of patients with atopic dermatitis （AD） and to evaluate the effects of tacrolimus on the expression.Methods Six patients with acute moderate or severe AD were enrolled in this study and topically treated with tacrolimus 0.1% ointment twice daily for 3 weeks.Tissue samples were obtained from the lesions and non-lesional skin at least 10 cm away from the lesions before and after the 3-week treatment.Skin specimens from 6 normal human controls served as the control.Patients were evaluated at the baseline,1 and 3 weeks after the beginning of treatment for clinical symptoms and signs by visual analogue scale （VAS）,eczema area and severity index （EASI） and investigator＇s global assessment （IGA）.The expression of PAR-2 in tissue specimens were determined by immunohistochemistry.Results PAR-2 was expressed throughout the whole epidermis,especially in the granular layer,hair follicles,sweat glands,endothelial cells and nerve fiber-like structures.Before treatment,the expression level （mean optical density） of PAR-2 in keratinocytes was 4339.6 ± 115.8 in lesional skin of AD patients,significantly higher than that in non-lesional skin （4189.0 t 228.9,t =2.85,P 〈0.05） and in normal skin （3864.0 ± 237.3,t =4.31,P 〈 0.05）.After the 3-week treatment with tacrolimus ointment,the expression level of PAR-2 significant decreased to 3942.4 ± 176.6 in keratinocytes from lesional skin of patients with AD （t =4.55,P 〈 0.05）.The expression level of PAR-2 was positively correlated with VAS score for itch,EASI and IGA score in the patients.Conclusions The expression of PAR-2 is enhanced in keratinocytes of lesions from AD patients,and is positively correlated with itch and lesion severity.Topical tacrolimus may suppress the overexpression of PAR-2 in keratinocytes in lesional skin of AD.