外用贝美前列素联合他克莫司软膏治疗眶周白癜风临床与机制研究  

Clinical effect and mechanism of topical bimatoprost combined with tacrolimus in the treatment of periorbital vitiligo

作　　者：胡泰然[1] 雷铁池[1] 苗芳[1] 苏梦云 廖蕾 江珊[1] HU Tai-ran;LEI Tie-chi;MIAO Fang;SU Meng-yun;LIAO Lei;JIANG Shan(Department of Dermatology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院皮肤科,湖北武汉430060

出　　处：《临床皮肤科杂志》2021年第8期467-472,共6页Journal of Clinical Dermatology

基　　金：国家自然科学基金(81573028)资助项目。

摘　　要：目的:观察外用贝美前列素(bimatoporst,BimP)联合他克莫司软膏治疗眶周白癜风的疗效并探讨BimP促进复色的机制。方法:收集6例稳定期眶周白癜风患者,试验组外用0.03%他克莫司软膏联合0.03%BimP滴眼液,他克莫司组单用0.03%他克莫司,2个月后比较复色率。豚鼠(n=6)背部剃毛后分区域处理,生理盐水组、BimP组分别予生理盐水和0.03%BimP外用,308 nm准分子光(308 nm EL)组予308 nm EL照射;Fontana-Masson染色计数黑素颗粒。C57小鼠右耳皮肤分组处理,BimP组、308 nm EL组和308 nm EL联合BimP组分别予0.03%BimP外用、308 nm EL照射及二者联合处理,左耳为对照;耳郭表皮DOPA染色计数阳性细胞;反转录(RT)-qPCR和western blot检测表皮酪氨酸酶表达水平。C57小鼠右耳用0.02%HC-030031[瞬时受体电位通道A1(TRPA1)阻滞剂]预处理,随后对双耳分组处理,对照组不处理,BimP组、长波紫外线(UVA)组、308 nm EL组分别予以0.03%BimP外用、UVA和308 nm EL照射。结果:临床观察显示试验组眶周白癜风皮损平均复色率高于他克莫司组(P<0.01)。豚鼠BimP组较生理盐水组有皮肤色素沉着增加和黑素颗粒增多(P<0.01)。小鼠耳郭模型中,BimP组表皮DOPA染色阳性细胞数和酪氨酸酶蛋白表达水平均高于对照组(P<0.01);HC-030031处理后,BimP组DOPA染色阳性细胞数较对照组明显减少(P<0.01)。结论:BimP对表皮黑素细胞的黑素生成活性有直接刺激作用,可能是联合他克莫司促白癜风皮损复色的机制。Objective:To investigate the clinical effect and potential mechanism of bimatoporst(BimP)combined with tacrolimus in the treatment of periorbital vitiligo.Methods:Six patients with stable periorbital vitiligo were recruited.The treatment group received topical administration of 0.03%BimP eye drops and 0.03%tacrolimus ointment,and the tacrolimus group was treated with 0.03%tacrolimus alone.Two months later,the patients′repigmentation was evaluated.The dorsal skin of six guinea pigs was shaved and divided into 3 regions,which were topically applied with normal saline(normal saline group),0.03%BimP(BimP group),or irradiated with 308 nm excimer light(308 nm EL group).The epidermal melanin particles were counted after Fontana-Masson staining.The right ears of mice were treated with topical administration of 0.03%BimP(BimP group),308 nm EL irradiation(308 nm EL group),or combined treatment(308 nm EL and BimP group),respectively.The left ears were used as control.The number of DOPA-positive cells in the auricle epidermis was counted.The transcription and protein expression levels of tyrosinase was detected by RT-qPCR and western blotting.In addition,the right ears of mice were pre-treated with 0.02%HC-030031(a specific blocker of transient receptor potential A1),and then treated with nothing(control group),topical administration of 0.03%BimP(BimP group),UVA irradiation(UVA group),and 308 nm EL irradiation(308 nm EL group).Results:Clinical data showed that the average repigmentation percentage of periorbital vitiligo patients in the treatment group was higher than that of the tacrolimus group(P<0.01).In guinea pigs,the melanin particles of BimP group were increased as compared with normal saline group(P<0.01).The number of DOPA-positive cells and tyrosinase protein expression level were both increased in BimP group as compared with the control group(P<0.01).After HC-030031 treatment,the number of DOPA-positive cells was significantly decreased in BimP group as compared with the control group(P<0.01).Conclusions:BimP di

关 键 词：贝美前列素 眶周白癜风 复色 黑素合成 瞬时受体电位通道A1 

分 类 号：R758.41[医药卫生—皮肤病学与性病学]