皮肤瞬时受体电位香草素-1和白细胞介素-31受体A在大疱性类天疱疮皮损组织中表达及意义

Expressions and significances of skin TRPV1 and interleukin-31 receptor A in bullous pemphigoid lesions

目的观察大疱性类天疱疮(bullous pemphigoid,BP)患者皮损组织瞬时受体电位香草素-1(transient receptor potential vanilloid 1,TRPV1)、白细胞介素-31受体A(interleukin-31 receptor A,IL-31RA)表达情况,探讨其在BP患者瘙痒发生中的作用。方法BP患者23例为BP组,整形外科手术患者12例为对照组,采用免疫组织化学法检测BP组皮损和对照组手术切除的正常皮肤表皮和真皮组织TRPV1、IL-3IRA表达的累积光密度(integrated optical density,IOD)值。采用瘙痒视觉模拟评分(visual analogue scale,VAS)评估BP患者瘙痒程度,比较不同瘙痒程度的BP患者瘙痒VAS评分及皮损表皮和真皮组织TRPV1、IL-3IRA表达的IOD值,采用Spearman相关分析BP患者瘙痒VAS评分与皮损表皮和真皮组织TRPV1、IL-3IRA表达的相关性。结果BP患者TRPV1、IL-31RA主要在表皮组织表达,其中轻度瘙痒7例,中度瘙痒9例,重度瘙痒7例。BP组患者皮损表皮和真皮组织TRPV1[1284.92(601.43,1788.39)、225.84(62.46,258.58)]、IL-31RA[1049.43(903.86,1235.15)、290.74(256.21,480.84)]表达的IOD值均高于对照组[TRPV1250.03(210.75,294.53)、39.89(37.29,47.21),IL-31RA 281.67(248.85,310.64)、71.89(65.30,88.96)](P<0.05);轻、中、重度瘙痒的BP患者瘙痒VAS评分依次增高[4.00(4.00,4.00)、5.00(5.00,5.50)、7.00(7.00,7.00)](P<0.05),皮损表皮组织TRPV1表达的IOD值[1885.62(1788.39,1973.68)、1284.92(1186.16,1558.39)、568.39(550.53,601.43)]依次降低(P<0.05),IL-31RA表达的IOD值[856.87(779.32,903.86)、1099.74(980.90,1190.52)、1374.18(1153.95,1507.45)]依次增高(P<0.05);轻、中、重度瘙痒的BP患者皮损真皮组织TRPV1、IL-31RA表达的IOD值[258.58(225.84,264.72)、256.04(217.74,268.15)、40.76(35.29,62.46),490.74(480.84,521.68)、290.46(248.53,331.69)、256.91(247.03,278.02)]均依次降低(P<0.05)。BP患者瘙痒VAS评分与皮损表皮组织TRPV1表达呈负相关(r=—0.910,P=0.023),与皮损表皮组织IL-31RA表达呈正相关(r=0.770,P=0.014);与皮损真皮组织TRPV1、IL-31RA表达均呈负相关(r=—0.790,P=0.018;r=—0.720,P=0.026)。结论BP患者皮损表皮和真皮组织TRPV1和IL-31RA表达均明显升高,参与瘙痒的发生;表皮和真皮组织TRPV1、真皮组织IL-31RA负反馈参与瘙痒的维持。

Objective To observe the expressions of transient receptor potential vanilloid 1(TRPV1)and interleukin-31 receptor A(IL-31 RA)in skin lesions of patients with bullous pemphigoid(BP),and to explore their roles in the pathogenesis of pruritus.Methods Twenty-three patients with BP were selected as BP group and another 12 patients receiving plastic surgery were as controls(control group).The integrated optical density(IOD)values of TRPV1 and IL-31 RA in the epidermis and dermis of skin lesions in BP group and of normal skin in control group were detected by immunohistochemical method.The pruritus degree in BP group was evaluated by visual analogue scale(VAS),and the VAS scores and IOD values of TRPV1 and IL-31 RA in the epidermis and dermis of BP patients with different pruritus degrees were compared.Spearman correlation was used to analyze the correlation between the VAS score and the expressions of TRPV1 and IL-31 RA in the epidermis and dermis of BP patients.Results TRPV1 and IL-31 RA were mainly expressed in the epidermis of BP patients.In 23 BP patients,there were 7 cases of mild pruritus,9 cases of moderate pruritus and 7cases of severe pruritus.The IOD values of TRPV1[1284.92(601.43,1788.39),225.84(62.46,258.58)]and IL-31 RA[1049.43(903.86,1235.15),290.74(256.21,480.84)]in the pidermis and dermis of skin lesions in BP group were higher than those in control group[250.03(210.75,294.53),39.89(37.29,47.21);281.67(248.85,310.64),71.89(65.30,88.96)](P<0.05).The VAS scores[4.00(4.00,4.00),5.00(5.00,5.50),7.00(7.00,7.00)]increased gradually in turn(P<0.05),the IOD values of TRPV1 in the epidermis[1885.62(1788.39,1973.68),1284.92(1186.16,1558.39),568.39(550.53,601.43)]decreased gradually in turn(P<0.05),and the IOD values of IL-31 RA[856.87(779.32,903.86),1099.74(980.90,1190.52),1374.18(1153.95,1507.45)]increased gradually in turn in BP patients with mild,moderate and severe pruritus(P<0.05).The IOD values of TRPVI and IL-31RA in the dermis decreased gradually in turn in BP patients with mild,moderate and severe pruritus[258.58(225.84,264.72),256.04(217.74,268.15),40.76(35.29,62.46);490.74(480.84,521.68),290.46(248.53,331.69),256.91(247.03,278.02)](P<0.05).The VAS score was negatively correlated with the expression of TRPVI in the epidermis of BP patients(r=-0.910,P=0.023),and positively correlated with the expression of IL-31 RA in the epidermis(r=0.770,P=0.014).The VAS score of pruritus was negatively correlated with the expressions of TRPV1 and IL-31 RA in the dermis of BP patients(r=-0.790,P=0.018;r=-0.720,P=0.026).Conclusions The expressions of TRPV1 and IL-31 RA in the epidermis and dermis of BP patients increase obviously,and are involved in pruritus.TRPV1 in the epidermis and dermis and IL-31 RA in the dermis may negatively regulate the maintenance of pruritus.