中华皮肤科杂志 ›› 2014, Vol. 47 ›› Issue (9): 654-658.

• 论著 • 上一篇    下一篇

苯烯莫德对变应性接触性皮炎BALB/c小鼠模型的影响

钱佳丽1,1,徐宏俊2,赵琰3,孙青苗3,马晓蕾4,黄海艳3,张建中4   

  1. 1. 北京市顺义区中医医院
    2. 北京市民航总医院皮肤科
    3. 北京大学人民医院
    4. 北京大学人民医院皮肤科
  • 收稿日期:2013-12-04 修回日期:2014-04-17 出版日期:2014-09-15 发布日期:2014-09-01
  • 通讯作者: 张建中 E-mail:rmzjz@126.com

Effect of benvitimod on allergic contact dermatitis in BALB/c mice

  • Received:2013-12-04 Revised:2014-04-17 Online:2014-09-15 Published:2014-09-01

摘要: 目的 探讨苯烯莫德对小鼠变应性接触性皮炎模型的疗效。 方法 用2,4-二硝基氟苯对BALB/c小鼠进行皮肤致敏和激发,分别建立急性和慢性小鼠接触性皮炎模型。将实验小鼠分为7组,分别为正常对照组、无水乙醇组、苯烯莫德0.5%、1.0%、2.0% 3个不同剂量组、0.1%地塞米松组和0.1%他克莫司组(n = 6)。观察外用苯烯莫德的疗效,包括对小鼠耳廓肿胀程度(包括双耳质量差与厚度差的变化)、病理学改变及皮损组织炎症细胞计数的影响;用药结束时评价苯烯莫德的用药安全性。 结果 在急性接触性皮炎模型中,苯烯莫德在24 h内的治疗作用不明显;0.5%、1.0%、2.0% 3个不同剂量组双耳质量差与基质对照组相比,差异均无统计学意义(均P > 0.05);双耳厚度差与基质对照组相比,差异亦无统计学意义(P > 0.05)。在慢性接触性皮炎模型中,苯烯莫德可明显缓解耳部肿胀程度,0.5%、1.0%、2.0% 3个不同剂量组苯烯莫德外用3周后,双耳质量差[(2.33 ± 0.45) mg,(2.30 ± 0.57) mg,(2.38 ± 0.27) mg]与基质对照组[(3.73 ± 0.33) mg]相比显著降低,差异均有统计学意义(均P < 0.01);双耳厚度差[(71.50 ± 3.15) × 10-3 mm,(75.50 ± 3.02) × 10-3 mm,(69.50 ± 2.59) × 10-3 mm]与基质对照组[(91.83 ± 2.04) × 10-3 mm]相比显著降低,差异均有统计学意义(均P < 0.01)。无论是急性接触性皮炎模型还是慢性接触性皮炎模型,3个不同剂量苯烯莫德均能显著降低耳部皮损组织炎症细胞浸润(均P < 0.01)。 结论 外用苯烯莫德对2,4-DNFB所致的小鼠慢性变应性接触性皮炎具有抑制作用,对急性模型效果不明显;未监测到局部药物不良反应。

关键词: 苯烯莫德, 皮炎,变应性接触性, 模型,动物

Abstract: Qian Jiali, Xu Hongjun, Zhao Yan, Sun Qingmiao, Ma Xiaolei, Huang Haiyan, Zhang Jianzhong*. *Department of Dermatology, Peking University People′s Hospital, Beijing 100044, China Corresponding author: Zhang Jianzhong, Email: rmzjz@126.com 【Abstract】 Objective To evaluate the efficacy of benvitimod on allergic contact dermatitis (ACD) in a mouse model of allergic contact dermatitis. Methods Acute and chronic ACD models were established respectively in 42 BALB/c mice through 2,4-dinitrofluorobenzene (DNFB) sensitization and challenge. Then, the BALB/c mice were equally divided into 7 groups with 6 mice in every group: normal control group receiving no treatment, five treatment groups topically treated with 0.1% dexamethasone solution, 0.1% tacrolimus (FK506) solution, 0.5% benvitimod solution, 1.0% benvitimod solution and 2.0 % benvitimod solution respectively, and dehydrated alcohol group treated with dehydrated alcohol only. All the drug solutions were topically applied at 24 and 36 hours after the last challenge in the murine models of acute ACD which were sacrificed at 48 hours, and twice daily from day 7 to 21 after the initial sensitization in the murine models of chronic ACD which were sacrificed on day 21 after the first topical treatment. Ear tissues were obtained from these mice and subjected to measurement of ear thickness and weight, as well as pathological examination and evaluation of inflammatory infiltrate by hematoxylin-eosin (HE) staining. The safety of these drugs was also estimated at the end of treatment. Results In the murine models of acute ACD, benvitimod showed no obvious therapeutic effect at 24 hours, with no significant differences in bilateral difference in ear thickness or weight between the three benvitimod groups and dehydrated alcohol group (all P > 0.05). Meanwhile, in the murine models of chronic ACD, benvitimod markedly decreased the swelling degree of ears, with significant differences between the three benvitimod groups (0.5%, 1.0% and 2.0% ) and dehydrated alcohol group in bilateral difference in ear thickness ((71.50 ± 3.15) × 10-3 mm,(75.50 ± 3.02) × 10-3 mm and(69.50 ± 2.59) × 10-3 mm vs. (91.83 ± 2.04) × 10-3 mm, all P < 0.01) and weight ((2.33 ± 0.45) mg, (2.30 ± 0.57) mg and (2.38 ± 0.27) mg vs. (3.73 ± 0.33) mg, all P < 0.01) after 3 weeks of treatment. The inflammatory infiltration in ear tissue was significantly attenuated in murine models of both acute and chronic ACD by the three concentrations of benvitimod compared with dehydrated alcohol (all P < 0.01). Conclusions Topical benvitimod can inhibit chronic ACD in mice induced by 2,4-DNFB, but exhibits no obvious effect on acute ACD. No apparent local adverse effects were observed during the treatment with benvitimod in these mice.

Key words: Benvitimod, Dermatitis, allergic contact, Disease models, animal

中图分类号: 

  • R751