氟芬那酸丁酯抑制紫外线诱导皮肤急性光毒性作用的研究

Inhibitory effect of butyl flufenamate on ultraviolet-induced acute skin phototoxicity

目的 探讨非甾体类抗炎药氟芬那酸丁酯（BT）对紫外线诱导皮肤急性光毒性反应的抑制作用及可能的作用机制.方法 SKH-1无毛小鼠背部随机编号分为6组,仅照光组、BT＋照光组、照光＋BT组、基质＋照光组、照光＋基质组、空白组.在处理后24 h收集各组皮肤标本,HE染色,用实时PCR检测caspase 3、p53、COX-2、PGER1、IL-1β、IL-6的表达量以及免疫荧光检测caspase 3的表达量.结果 照光后24 h,与仅照光组相比,涂抹BT软膏组皮肤水肿程度减轻,凋亡细胞的数目减少.实时PCR显示：与空白组相比,仅照光组caspase 3、p53、COX-2、PGER1、IL-1β、IL-6均有升高（P＜0.05）;BT软膏＋照光组与仅照光组比较,caspase 3、p53、COX-2、PGER1、L-1β、IL-6表达明显下调（P＜0.05）,照光＋BT软膏组仅caspase 3、p53的表达明显下调（P＜0.05）.免疫荧光检测：仅照光组与空白组相比caspase 3表达明显上调;与仅照光组比较,BT软膏＋照光组和照光＋ BT软膏组caspase 3表达显著下降.结论 BT可以部分抑制紫外线对于SKH-1无毛小鼠皮肤造成的急性光毒作用.

Objective To evaluate the inhibitory effect of butyl flufenamate （BT） on ultraviolet （UV）-induced acute skin phototoxic reaction,and to investigate its possible mechanisms.Methods Eight SKH-1 hairless mice were included in this study.The back of each SKH-1 hairless mouse was divided into six regions,which were then randomly classified into six groups：blank group receiving no treatment,UV group receiving UV radiation only,BT ＋ UV group and vehicle ＋ UV group topically treated with BT ointment and vehicle respectively followed by UV radiation,UV ＋ BT group and UV ＋ vehicle group topically treated with BT ointment and vehicle respectively after UV radiation.Skin samples were obtained from these mice at 24 hours after treatment.Subsequently,hematoxylin-eosin （HE） staining was performed,real-time PCR was carried out to detect mRNA expressions of caspase-3,p53,COX-2,PGER1,interleukin （IL）-1β,IL-6,and an immunofluorescence assay was conducted to observe the expression of caspase-3.Statistical analysis was carried out by repeated-measures analysis of variance （ANOVA）.Results Compared with the UV group,both BT ＋ UV group and UV ＋ BT group showed a decrease in the degree of skin edema and number of apoptotic cells at 24 hours after UV radiation.Real-time PCR showed that the mRNA expressions of caspase-3,p53,COX-2,PGER1,IL-l β and IL-6 were significantly higher in the UV group than in the blank group （all P 〈 0.05）,but significantly lower in the BT ＋ UV group than in the UV group （all P 〈 0.05）,and only the expressions of caspase-3 and p53 mRNAs were significantly decreased in the UV ＋ BT group compared with the UV group （both P 〈 0.05）.The immunofluorescence assay revealed that the expression of caspase-3 increased in the UV group compared with the blank group,but decreased in both BT ＋ UV group and UV ＋ BT group compared with the UV group.Conclusion BT could partially inhibit UV-induced acute skin phototoxicity in SKH-1 hairless mice.