摘要
目的通过观察全反式维A酸(at-RA)及其受体激动剂和拮抗剂对ICR小鼠光老化模型中真皮胶原降解的影响,探讨at-RA抗皮肤光老化的作用机制。方法用UVA,UVB照射ICR小鼠16周,构建光老化动物模型并分组,分别用at-RA,维A酸受体(RAR)/维A酸类受体(RXR)的激动剂/拮抗剂干预,通过MASSON染色观察各组小鼠的胶原纤维改变,免疫组化方法检测基质金属蛋白酶(MMP-1和MMP-3)表达。结果①与正常对照组相比,光老化模型组的胶原表达减少,MMP-1和MMP-3表达增多,差异具有统计学意义(P<0.05)。②与模型组相比,at-RA组、RAR选择性激动剂组胶原表达增多,MMP-1和MMP-3表达减少,差异均具有统计学意义(P<0.05);而RXR激动剂组与模型组的差异无统计学意义(P>0.05)。③at-RA+RAR拮抗剂组与at-RA的MMP-1和MMP-3表达差异具有统计学意义(P<0.05);at-RA+RXR拮抗剂组与at-RA组的表达差异无统计学意义(P>0.05);RAR激动剂+RAR拮抗剂组与RAR激动剂组的表达差异具有统计学意义(P<0.05)。结论 at-RA可通过抑制基质金属蛋白酶表达从而减少胶原降解,在此过程中RAR可能起着关键作用。
Objective To investigate the mechanism whereby all-trans retinoic acid （at-RA） inhibits photoaging by e- valuating the effects of RA receptor antagonist and agonist on the collagen degradation in vivo. Methods Photoaging model was established by irradiating ICR mice with UBV and UVA for 16 weeks. Following topical treatment with at-RA, RAR（ retinoic acid receptor） or RXR（ retinoid X receptor） agonist/antagonists, the changes in collagen fibers were observed by MASSON staining and the expression levels of matrix metallopro- teinases（ MMP-1 and MMP-3） were assessed by immunohistochemistry. Results In comparsion with normal controls,reduced collagen and increased MMPs expression were evident in photoaging skin（P 〈0.05 ）. Both at-RA and RAR agonists significantly increased collagen and decreased matrix metalloproteinases （P 〈 0. 05 ）. In contrast, the levels of collagen and MMPs were no differences between RXR agonist-treated mice and controls. Moreover, RAR antagonists prevented RAR induced the changes in MMPs expression, whereas RXR antagonists had no effect on RAR induced the changes in MMPs expression. Additionally, RAR antago- nists prevented RAR agonist-induced the changes in MMPs expression （P 〈 0. 05 ）. Conclusion At-RA-in- duced reduction in collagen degradation results from inhibition of MMPs（ MMP-1 and MMP-3） and is media- ted via RAR receptor.
出处
《中国皮肤性病学杂志》
CAS
北大核心
2014年第3期221-225,共5页
The Chinese Journal of Dermatovenereology
基金
国家自然科学基金资助项目(81271741)
关键词
光老化
全反式维A酸
RAR
RXR
胶原
基质金属蛋白酶
Photoaging
all-trans retinoic acid
Retinoic acid receptor
Retinoid X receptor
Collagen
Matrix metallo-proteinases
