中华皮肤科杂志 ›› 2008, Vol. 41 ›› Issue (12): 818-820.

• 论著 • 上一篇    下一篇

特应性皮炎患者瘙痒性皮损中神经形态变化及蛋白酶活化受体2的表达

倪春雅 刘玲玲 窦侠 弓月 朱学骏   

  1. 北京大学第一医院皮肤科 北京大学第一医院皮肤科 北京大学第一医院皮肤科 北京大学第一医院皮肤科 北京大学第一医院皮肤科
  • 收稿日期:2007-12-28 修回日期:2008-08-13 发布日期:2008-12-15
  • 通讯作者: 倪春雅 E-mail:woodstock-27@hotmail.com

Cutaneous nerve morphology and protease activated receptor 2 expression in pruritic skin lesions of atopic dermatitis

  

  • Received:2007-12-28 Revised:2008-08-13 Published:2008-12-15

摘要: 目的 探讨皮肤神经及蛋白酶活化受体2(PAR2)在特应性皮炎瘙痒发生中的作用。方法 取特应性皮炎患者(7例)慢性期瘙痒性皮损及正常人(7例)皮肤,用真皮单片制备技术,免疫荧光双染标记,比较皮损与正常皮肤中神经形态变化及PAR2表达。结果 特应性皮炎患者皮损及正常人皮肤蛋白基因产物9.5(PGP9.5)/PAR2及P物质(SP)/PAR2免疫荧光双染均呈阳性表达,阳性部分基本重叠。与正常皮肤比较,瘙痒性皮损中PGP9.5阳性神经纤维总长度增加,直径增大(P < 0.05),SP阳性神经纤维总长度没有明显变化(P > 0.05),但直径增大(P < 0.05);瘙痒性皮损中PAR2和SP免疫荧光的累积光密度值增加(P < 0.05)。结论 特应性皮炎慢性期瘙痒性皮损中出现神经纤维明显增生,PAR2及SP在神经上的表达上调,提示蛋白酶-PAR2通路的信号增强可能与特应性皮炎患者皮肤瘙痒的机制有关。

关键词: 皮炎, 特应性;瘙痒症;神经纤维;受体, PAR-2

Abstract: Objective To study the role of cutaneous nerve and protease activated receptor 2 (PAR2) in the development of pruritus in atopic dermatitis (AD). Methods Dermal sheets were prepared from chronically pruritic skin lesions of 7 patients with AD, as well as from the normal skin of 7 healthy human controls. Double labeled immunofluorescence was performed using mouse anti-protein gene product 9.5 (PGP9.5) monoclonal antibody and rabbit anti-substance P (SP) polyclonal antibody to observe the morphological changes in cutaneous nerve fibers, and Image-Pro Plus 6 software was used to semiquantitively assess the length, diameter of nerve fibers, integral optimal density of PAR2 and SP in dermal sheets. Results Immunofluoresence double staining showed that PAR2 co-expressed with PGP9.5 or SP in cutaneous nerve fibers. Compared with the normal control skin, both the total length and average diameter of PGP 9.5- expressing nerve fibers were increased (11051.8 ± 1900.9 μm vs 7264.0 ± 2659.9 μm, 4.23 ± 0.15 μm vs 3.95 ± 0.15 μm, both P < 0.01) in pruritic lesions, while only the average diameter of SP-expres- sing nerve fibers was up-regulated (3.99 ± 0.20 μm vs 3.80 ± 0.07 μm, P < 0.05), and the total length of them remained unchanged (4304.7 ± 1455.0 μm vs 3380.0 ± 1735.4 μm, P > 0.05). Also, increased integral optimal density was observed for SP and PAR in pruritic lesions in comparison with the normal control skin (27.71 ± 16.52 vs 12.63 ± 4.31, 35.99 ± 8.63 vs 22.69 ± 9.56, both P < 0.05). Conclusion Our results indicate a hyper- plasia of cutaneous nerve fibers in chronic itchy skin lesions of AD and an increase in the expression of PAR2 and SP in the cutaneous nerve fibers, suggesting that the signal enhancement in PAR2 pathway may be related to the mechanism of pruritus in patients with AD.