Chen S, Kiss I, Tramposch K M
Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Buffalo, NY 14213.
J Invest Dermatol. 1992 Feb;98(2):248-54. doi: 10.1111/1523-1747.ep12556066.
The effects of all-trans retinoic acid (t-RA) on photodamaged and normal non-irradiated skin were examined in hairless mice (Skh:HR-1). After being exposed to increasing doses of UVB for 10 weeks (total dose = 1.4 J/cm2), the animals were then treated with 0.1% t-RA in ethanol (50 microliters, five times per week) for another 10 weeks. Several animals (the follow-up group) were further observed after the termination of the t-RA treatment to investigate if the t-RA effect was reversible. Wrinkle effacement induced by t-RA was compared with three other parameters: a) de novo collagen synthesis, b) width of the dermal repair zone, and c) epidermal thickening. Interestingly, t-RA did not stimulate collagen synthesis in animals not exposed to UVB. In the irradiated animals, the time course of wrinkle reduction correlated with the stimulation of collagen synthesis. After a synchronous initial lag phase of 4-6 weeks, the wrinkling decreased from the maximum grade of 4 to a mean grade of 1.3, whereas collagen synthesis was enhanced to 245% of the control at week 10 of t-RA treatment. In contrast, a similar lag phase was not observed for either the appearance of the dermal repair zone or epidermal thickening. In the follow-up group, upon termination of t-RA treatment, collagen synthesis returned to the control level. Wrinkle effacement and thickening of the dermal repair zone, however, did not regress, suggesting the anti-photoaging effect of t-RA was not reversible over this time frame. The correlation between the length of the lag phases for collagen synthesis and wrinkle reduction points to the possibility that collagen plays an important role in tRA-induced wrinkle effacement. Both parameters are thus important endpoints for investigating the mechanism of RA-induced repair of photodamaged skin.
在无毛小鼠（Skh:HR-1）中研究了全反式维甲酸（t-RA）对光损伤皮肤和正常未受照射皮肤的影响。在接受递增剂量的UVB照射10周（总剂量 = 1.4 J/cm2）后，然后用0.1%的t-RA乙醇溶液（50微升，每周5次）再治疗10周。在t-RA治疗结束后，对几只动物（随访组）进行进一步观察，以研究t-RA的作用是否可逆。将t-RA诱导的皱纹消除与其他三个参数进行比较：a）新生胶原蛋白合成，b）真皮修复区宽度，c）表皮增厚。有趣的是，t-RA在未暴露于UVB的动物中不刺激胶原蛋白合成。在受照射的动物中，皱纹减少的时间进程与胶原蛋白合成的刺激相关。在同步的初始滞后阶段4 - 6周后，皱纹从最高等级4降至平均等级1.3，而在t-RA治疗第10周时胶原蛋白合成增强至对照的245%。相比之下，真皮修复区的出现或表皮增厚均未观察到类似的滞后阶段。在随访组中，t-RA治疗结束后，胶原蛋白合成恢复到对照水平。然而，皱纹消除和真皮修复区增厚并未消退，表明在这个时间范围内t-RA的抗光老化作用是不可逆的。胶原蛋白合成和皱纹减少的滞后阶段长度之间的相关性表明胶原蛋白在tRA诱导的皱纹消除中可能起重要作用。因此，这两个参数都是研究RA诱导的光损伤皮肤修复机制的重要终点。
