他扎罗汀和全反式维A酸对热休克后的成纤维细胞表达金属基质蛋白酶及其抑制剂的研究

Effects of all-trans retinioic acid and tazarotene on MMP-1 and TIMP-1 expression in cultured human fibroblasts after heat shock

目的观察维A酸(他扎罗汀和全反式维A酸)对体外培养的成纤维细胞热休克后,表达基质金属蛋白酶(MMP-1)和基质金属蛋白酶组织抑制因子(TIMP-1)的影响,探讨他扎罗汀和全反式维A酸对热休克后的真皮发生作用的分子生物学机制。方法体外培养的成纤维细胞在43℃水浴中热休克30min后,加入不同浓度的维A酸,24h后应用ELISA法上清液检测MMP-1和TIMP-1表达,并与对照组比较。结果维A酸类药物作用于热休克后的成纤维细胞,可减少MMP-1,同时增加其抑制剂TIMP-1的含量。其中,他扎罗汀的效果优于全反式维A酸。结论维A酸类药物对热休克后成纤维细胞产生的,在皮肤老化中有重要作用的MMP-1及其抑制剂TIMP-1有调节作用,可能对修复热休克导致的真皮基质改变有积极作用。

Objective To investigate the molecular mechanism of dermal damage in heat shock-induced skin aging by observing the expressions of metalloproteinase-1 （MMP-1） and tissue inhibitor of MMP-1 （TIMP-1） in retinoic acid-treated cultured human fibroblasts with heat shock. Methods Cultured human fibroblasts were treated with tazarotene or all-trans-retinioic acid （at-RA） after heat shock for 30 min in 43 ℃ water bath. Twenty-four hours later, MMP-1 and TIMP-1 contents in the supematant of the cell cult-are medium were measured using enzyme-linked immunosorbent assat （ELISA）. Results Both tazarotene and at-RA dose-dependently reduced the expression of MMP-1 and increased the expression of TIMP-1 in cultured human fibroblasts exposed to heat shock, and tazarotene produced stronger effect than at-RA. Conclusion Retinoic acid can reduce the expression of MMP-1 and increase the expression of TIMP-1 in cultured human fibroblasts, suggesting its therapeutic potential for heat shock-induced skin aging.