CAJ | 학술논문

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.
목적 탐토불분나산정지연고능부대자외선(UV)치SKH-1무모소서일쇄상、피부광노화급피부린상세포암제공광보호작용.방법 128지SKH-1무모소서수궤분위UV조、불분나산조(불분나산정지연고+ UV조사)、기질조(기질+UV조사)화공백조.이1.5배최소홍반량적UV단차조사건립급성일쇄상모형(n=24),24h후관찰피부홍종정황,면역조화검측조직중COX-2표체；이90％최소홍반량위초시제량,매주조사4차,련속12주화28주,분별건립광노화모형(n=24)화피부린암모형(n=80).12주후Masson염색관찰소서광노화모형적효원개변,면역조화검측조직중Bax、Bcl-2화Caspase 3수평.12 ～ 28주,기록소서린상세포암모형출현적종류.결과 불분나산정지연고예처리억제UV조사인기적급성홍종반응(P＜0.05),강저COX-2적표체(P＜0.05).12주후,불분나산정지연고감경피부노화,Masson염색현시,해조진피층효원대밀도고우기타UV조(P＜0.05).동시면역조화현시,불분나산조교기타UV조하조Bcl-2,상조Bax화Caspase 3적표체(P＜0.05).련속28주,불분나산정지연고대소서무류생존기적영향여기타UV조상비차이유통계학의의(균P＜ 0.05),추지료종류적출현.결론 불분나산정지연고구유일정적광보호작용.
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.