EVALUATION OF TOPICAL RETINOIDS FOR CUTANEOUS PHARMACOLOGICAL ACTIVITY IN YUCATAN MICROSWINE
EVALUATION OF TOPICAL RETINOIDS FOR CUTANEOUS PHARMACOLOGICAL ACTIVITY IN YUCATAN MICROSWINE
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DOI：
10.1007/bf00371741
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发表时间：
1995-09-01
影响因子：
3
通讯作者：
MEZICK, JA
中科院分区：
文献类型：
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作者：
GENDIMENICO, GJ;LIEBEL, FT;MEZICK, JA
类维生素A对皮肤的药理学作用主要在使用小动物（如小鼠和兔）的试验系统中进行了研究。由于小动物和人类之间皮肤渗透和代谢的潜在显著差异，我们使用尤卡坦微型猪作为测试局部类维生素A的替代模型。微型猪的皮肤在功能和解剖学上与人类皮肤相似，比大多数其他物种更接近。在这些研究中，用类维生素A每周连续5天局部处理微型猪皮肤，持续5周。我们发现微型猪表皮对类维生素A有功能性反应，因为它经历增生并显示出经表皮水分损失（TEWL）的增加。全反式维甲酸及其类似物13-顺式维甲酸、4-羟基维甲酸和4-氧代维甲酸均引起表皮增厚和TEWL增加。这三种类似物的效力低于全反式维甲酸。合成类维生素A，TTNPB，强效诱导表皮增生和增加TEWL，但结构相似，间羧基TTNPB，这也是核视黄酸受体无活性，是没有影响的微型猪表皮。这些发现表明，微型猪可用于评价局部类维生素A的皮肤效应。该模型可用于鉴定具有潜在临床活性的类维生素A。
The pharmacological effects of retinoids on skin have been studied primarily in test systems using small animals, such as mice and rabbits, Because of potentially significant differences in skin permeation and metabolism between small animals and humans, we have used Yucatan microswine as an alternative model for testing topical retinoids. Microswine skin resembles human skin, functionally and anatomically, more closely than most other species. In these studies, microswine skin was treated topically with retinoids for 5 consecutive days per week for 5 weeks. We found microswine epidermis to be functionally responsive to retinoids in that it undergoes hyperplasia and shows an increase in transepidermal water loss (TEWL). All-trans-retinoic acid, and its analogs, 13-cis-retinoic acid, 4-hydroxy-retinoic acid and 4-oxo-retinoic acid all caused epidermal thickening and increased TEWL. The three analogs were less potent than all-trans-retinoic acid. A synthetic retinoid, TTNPB, potently induced epidermal hyperplasia and increased TEWL, but a close stuctural analog, m-carboxy-TTNPB, which is also inactive on nuclear retinoic acid receptors, was without effects on microswine epidermis. These findings show that microswine are useful for evaluating the cutaneous effects of topical retinoids. This model could be of value in identifying retinoids with potential clinical activity.