克立硼罗软膏调节角质形成细胞异常活化缓解小鼠银屑病作用  

Crisaborole ointment regulates abnormal activation of keratinocytes and relieves psoriasis in mice

作　　者：桂雨晴 唐彩红 陈镜宇[1] 姜玲[1,2] 魏伟[1] Gui Yuqing;Tang Caihong;Chen Jingyu;Jiang Ling;Wei Wei(Institute of Clinical Pharmacology of Anhui Medical University,Hefei 230032;The First Affiliated Hospital of University of Science and Technology of China,Hefei 230001)

机构地区：[1]安徽医科大学临床药理研究所,合肥230032 [2]中国科学技术大学附属第一医院,合肥230001

出　　处：《安徽医科大学学报》2023年第5期735-741,共7页Acta Universitatis Medicinalis Anhui

基　　金：安徽高校自然科学研究项目(编号:KJ2019A0263)。

摘　　要：目的明确克立硼罗软膏(Cri)外用对咪喹莫特(IMQ)诱导小鼠银屑病的治疗作用与机制。方法用Balb/c小鼠建立IMQ小鼠银屑病模型,分为Cri(7.5、15、30 mg/cm^(2))组、卤米松(15 mg/cm^(2))组、模型组及正常组。对小鼠皮损进行银屑病面积和严重程度指数(PASI)评分,HE染色观察表皮病理变化;免疫组化测定皮损处角蛋白的表达;检测皮损处皮肤环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、磷酸化-cAMP反应元件结合蛋白(p-CREB)水平。结果与模型组相比,Cri组小鼠皮肤鳞屑、红斑和增厚减轻,PASI评分降低,皮损处增殖角蛋白(K)6、K16、K17表达水平降低(F=12.62、19.41、28.39,P<0.01),而分化角蛋白K1、K10表达水平增加(F=27.95、9.64,P<0.01)。Cri能提升小鼠皮损处皮肤中cAMP、PKA水平,增加p-CREB的表达。结论Cri可能通过调节角质形成细胞异常增殖和分化发挥对IMQ诱导的小鼠银屑病的治疗作用。Objective To study the effect of crisaborole on imiquimod(IMQ)-induced psoriasis in mice.Methods Forty eight Balb/c mice were randomly divided into crisaborole group(7.5,15,30 mg/cm^(2)),halometasone group(15 mg/cm^(2)),model group and normal group.IMQ was applied to the back of mice to establish the psoriasis model.Psoriasis area and severity index(PASI)score was calculated,pathological changes,skin epidermal thickness and inflammatory cell infiltration in the dermis were observed by HE staining.The expressions of keratin(K)1,K10,K6,K16 and K17 in skin lesions were detected by Western blot and immunohistochemistry.The levels of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phospho-cAMP response element binding protein(p-CREB)were detected.Results Compared with the model group,the PASI score of the crisaborole group decreased,the expression levels of proliferative keratin(K6,K16 and K17)decreased(F=12.62、19.41、28.39,P<0.01),and the expression levels of differentiation keratin(K1 and K10)increased(F=27.95、9.64,P<0.01).Conclusion Crisaborole plays a therapeutic role in IMQ-induced psoriasis in mice by regulating the abnormal proliferation and differentiation of keratinocytes.

关 键 词：银屑病 克立硼罗 增殖 分化 角质细胞 PKA CREB 

分 类 号：R967[医药卫生—药理学]