氟芬那酸丁酯软膏对SKH-1无毛小鼠的光保护作用

摘要/Abstract

摘要： 【摘要】目的探讨氟芬那酸丁酯软膏能否对紫外线（UV）致SKH-1无毛小鼠日晒伤、皮肤光老化及皮肤鳞状细胞癌提供光保护作用。方法 128只SKH-1无毛小鼠随机分为UV组、氟芬那酸组（氟芬那酸丁酯软膏 + UV照射）、基质组（基质 + UV照射）和空白组。以1.5倍最小红斑量的UV单次照射建立急性日晒伤模型（n = 24），24h后观察皮肤红肿情况，免疫组化检测组织中COX-2表达；以90%最小红斑量为初始剂量，每周照射4次，连续12周和28周，分别建立光老化模型（n = 24）和皮肤鳞癌模型（n = 80）。12周后 Masson染色观察小鼠光老化模型的胶原改变，免疫组化检测组织中Bax、Bcl-2和Caspase 3水平。12 ~ 28周，记录小鼠鳞状细胞癌模型出现的肿瘤。结果氟芬那酸丁酯软膏预处理抑制UV照射引起的急性红肿反应（P ＜ 0.05），降低COX-2的表达（P ＜ 0.05）。12周后，氟芬那酸丁酯软膏减轻皮肤老化，Masson染色显示，该组真皮层胶原带密度高于其他UV组（P ＜ 0.05）。同时免疫组化显示，氟芬那酸组较其他UV组下调Bcl-2，上调Bax和Caspase 3的表达（P ＜ 0.05）。连续28周，氟芬那酸丁酯软膏对小鼠无瘤生存期的影响与其他UV组相比差异有统计学意义（均P ＜ 0.05），推迟了肿瘤的出现。结论氟芬那酸丁酯软膏具有一定的光保护作用。【关键词】氟芬那酸丁酯软膏；紫外线；光；晒伤；小鼠

关键词: 晒伤, 氟芬那酸丁酯, 紫外线, 光, 小鼠

Abstract: LV Ting*, TU Qing-feng, WANG Xiu-li, WANG Hong-wei. *Department of Dermatology, Huadong Hospital, Fudan University, Shanghai 200040, China Corresponding author: WANG Hong-wei, Email: hongweiwang2005@aliyun.com 【Abstract】 Objective To investigate the protective effect of butyl flufenamate ointment against ultraviolet （UV）-induced skin damage, skin aging, and cutaneous squamous cell carcinoma （CSCC） in SKH-1 hairless mice. Methods A total of 128 mice were randomly and equally divided into four groups: UV group receiving UV irradiation only, butyl flufenamate ointment group and matrix cream group receiving UV irradiation after 30-minute pretreatment with topical butyl flufenamate ointment and matrix cream respectively, and blank control group receiving neither pretreatment nor irradiation. In the sunburn experiment （n = 24）, mice were exposed to single session of UV irradiation （1.5 minimal erythema doses （MEDs））, and 24 hours later, erythema and swelling response was observed, and skin tissue was obtained from the irradiated area on the back of mice followed by the determination of COX-2 expression using the streptavidin biotin peroxidase complex （SABC） method. To establish a photoaging （n = 24） and CSCC （n = 80） model, mice were exposed to four sessions of UV irradiation every week for 12 and 28 successive weeks respectively, with the irradiation dose starting at 0.9 MED and increasing gradually. After 12-week irradiation, skin tissue was resected from the back of photoaged mice and subjected to Masson staining for the evaluation of collagen changes as well as immunohistochemical analysis for the quantification of Bax, Bcl-2 and Caspase 3 expression. The initiation and progression of CSCC were observed in mice on a once-a-week basis from 12 to 28 weeks. SPSS 21.0 software was used for statistical analysis. One way analysis of variance was carried out for multiple-group comparisons of numerical data, Ridit analysis for the comparison of immunohistochemical staining intensity. Kaplan-Meier method and log-rank test were utilized for the comparison of tumor-free survival time. Results Both the degree of erythema and swelling response and expression level of COX-2 were significantly lower in the butyl flufenamate ointment group than in the other two UV-irradiated groups （all P < 0.05）. After 12-week irradiation, the butyl flufenamate ointment group showed milder degree of skin aging, together with higher density of collagen in dermis, weaker expression of Bcl-2 but stronger expression of Bax and Caspase 3, by comparison with the other two UV-irradiated groups （all P < 0.05 ）. During the 28 weeks of irradiation, the median tumor-free survival time was statistically longer in the butyl flufenamate ointment group than in the matrix cream group and UV group（（25.0 ± 0.4） months vs. （24.0 ± 0.3） months and （23.0 ± 0.4） months, P < 0.05 and 0.01 respectively）. Conclusion Butyl flufenamate ointment has a certain photoprotective effect. 【Key words】 Butyl flufenamate ointment; Ultraviolet rays; Light; Sunburn; Mice

吕婷涂庆峰王秀丽王宏伟. 氟芬那酸丁酯软膏对SKH-1无毛小鼠的光保护作用[J]. 中华皮肤科杂志, 2013, 46(10): 711-715.

参考文献

[1] 吕婷, 王秀丽, 周文江, 王宏伟, 缪飞, 李晶晶. 紫外线所致皮肤鳞状细胞癌小鼠模型的建立. 中华皮肤科杂志, 2011, 44(3):174-177. [2] 王家璧, 刘跃华. 氟芬那酸丁酯软膏在中国8年临床研究回顾. 中国皮肤性病学杂志 , 2010,24(8):689-691. Nonsteroidal Anti-in?ammatory Drug Use in thePrevention and Treatment of Squamous Cell Carcinoma [3] Kim TH, Ananthaswamy HN, Kripke ML, et al. Advantages of using hairless mice versus haired mice to test sunscreen efficacy against photoimmune suppressions. Photochem Photobiol. 2003,78(1):37-42. [4] Nelson AA, Miller AD, Fleischer AB, et al. how much of a topical agent should be prescribed for children of different sizes? J Dermatolog Treat. 2006,17(4):224-228. [5] Jiang H, Fine JP. Survival analysis. Methods Mol Biol. 2007;404:303-18. [6] Bennea MF，Robinson MK，Baron ED，et a1．Skin immune systems and inflammation：protector of the skin or promoter of aging[J]．J Invesfig Dermatol Syrup Proc，008，13(1)：15—19． [7] 刘霞. 氟芬那酸丁酯软膏治疗面部常见日光相关性皮肤病临床疗效分析. 临床皮肤科杂志. 2011,40(7):435-436. [8] Cole CA, Davies RE, Forbes PD, et al. comparison of action spectra for acute cutaneous response to ultraviolet radiation:man and albino hairless mouse. Photochem Photobiol. 1983 ,37(6):623-631. [9] Wilgus TA, Koki AT, Zweifel BS, et al. Inhibition of cutaneous ultraviolet light B-mediated inflammation and tumor formation with topical celecoxib treatment. Mol Carcinog. 2003 ,38(2):49-58. [10] Development of a treatment algorithm for actinic keratoses:a European consensus. [11] 何方 ,肖毅,陈洪铎等.非甾体抗炎药对中波紫外线诱导小鼠皮肤肿瘤影响的研究. 中国麻风皮肤病杂志. 2008,24(8):589-591. [12] Zhou XM, Wong BC, Fan XM, et al. Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. Carcinogenesis. 2001,22(9):1393-1397.

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