摘要
目的探讨全反式维A酸(at-RA)抑制光老化皮肤基质金属蛋白酶(MMP)-3和MMP-13表达的受体机制。方法中长波紫外线照射ICR小鼠12周,建立皮肤光老化动物模型,按照实验分组进行at-RA、维A酸受体(RAR)/维A酸X受体(RXR)的激动剂/拮抗剂干预后,HE染色观察皮肤组织病理学的改变;Western blot检测MMP-3和MMP-13的蛋白表达水平;碱水解法检测皮肤胶原蛋白的含量。结果与模型对照组相比,at-RA组、RAR激动剂组胶原蛋白含量增多,MMP-3和MMP-13表达量明显减少(P均<0.01),而RXR激动剂组与模型对照组的差异无统计学意义;at-RA/RAR激动剂+RAR拮抗剂组较at-RA/RAR激动剂组胶原蛋白含量减少,MMP-3和MMP-13表达量显著增多(P均<0.01),而at-RA+RXR拮抗剂组与at-RA组的差异无统计学意义。结论 at-RA可通过RAR下调MMP-3和MMP-13蛋白的表达,抑制光老化皮肤胶原的降解。
Objective To investigate the receptor mechanisms of all-trans retinoic acid (at-RA)-induced inhibition of matrix metalloproteinase (MMP)-3 and MMP-13 in photoaged skin. Methods The photoaged model was established by irradiation of ICR mice with UVA and UVB for 12 weeks. The photoaged mice were treated topically with at-RA, retinoic acid receptor (RAR) or retinoid X receptor (RXR) agonist/antagonist. HE staining was used to evaluate the histopathologic changes in the skin while expression levels of MMP-3 and MMP-13 protein were analyzed by Western blot. The collagen contents were measured by the method of alka- line hydrolysis. Results Compared with vehicle controls, the collagen contents were increased in mice treated with either at-RA or RAR agonist, while the expression levels of MMP-3 and MMP-13 were reduced significantly ( all P 〈 0. 01 ). In contrast, the expression levels of MMP-3 and MMP-13 were no significant differences between RXR agonist and vehicle controls. The collagen content was lower in mice treated with at-RA/RAR agonist plus RAR antagonist group than at-RA/RAR agonist treatment, whereas the expression levels of MMP-3 and MMP-13 were significantly higher in at-RA/RAR agonist plus RAR antagonist group than at-RA/RAR agonist treatment (all P 〈 0. 01 ). However, the expression levels of MMP-3 and MMP- 13 were no significant differences between at-RA plus RXR antagonist group and at-RA group. Conclusion At-RA inhibits the degradation of collagen via RAR to downregulate the expressions of MMP-3 and MMP-13 in photoaged skin.
出处
《中国皮肤性病学杂志》
CAS
CSCD
北大核心
2016年第9期890-894,共5页
The Chinese Journal of Dermatovenereology
基金
国家自然科学基金(81271741)
关键词
全反式维A酸
光老化
基质金属蛋白酶-3
基质金属蛋白酶-13
RAR
RXR
All-trans retinoie acid
Photoaging
Matrix metaUoproteinase-3
Matrix metalloproteinase-13
Retinoic acid receptor
Retinoid X receptor