盐酸普萘洛尔致银屑病样大鼠模型的剂量、时间及性别探讨  

Exploration of dose,time and sex in a psoriasis-like rat model caused by propranolol hydrochloride

作　　者：张萌萌 刘树民[1] 孙慧娟 高蕊 邓戈宇 张振东 黄琳 卢芳[1] ZHANG Mengmeng;LIU Shumin;SUN Huijuan;GAO Rui;DENG Geyu;ZHANG Zhendong;HUANG Lin;LU Fang(Institute of Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040)

机构地区：[1]黑龙江中医药大学中医药研究院,黑龙江哈尔滨150040

出　　处：《海南医科大学学报》2025年第5期351-359,372,共10页Journal of Hainan Medical University

基　　金：国家重点研发计划-中医药现代化(2022YFC3502100;2022YFC3502102;2022YFC3502102-04)。

摘　　要：目的:研究5%盐酸普萘洛尔乳膏剂在不同剂量、时间、性别下对银屑病样大鼠造模效果的影响。方法:将大鼠随机分为6组,雌性空白及高(2.7 g/4 cm^(2))、低(1.2 g/4 cm^(2))剂量组、雄性空白及高(2.7 g/4 cm^(2))、低(1.2 g/4 cm^(2))剂量组,将5%盐酸普萘洛尔乳膏剂均匀涂抹于大鼠背部皮肤上,每天1次,分别涂抹1周、2周,设立1个月恢复期。通过比较各组银屑病皮损面积和严重程度指数、HE染色、免疫组化法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和细胞角蛋白(cytokeratin-17,CK-17)表达水平、ELISA及RT-qPCR法检测大鼠炎症细胞因子表达,评价皮损严重程度及造模效果。结果:与空白组比较,造模1周和2周的雌雄高低剂量组大鼠出现明显红斑、鳞屑和肥厚,角化不全,表皮增厚,PCNA和CK-17表达增多,血清和皮损中的IL-1β、IL-17A、IL-22、IL-23和TNF-α表达量升高;与造模2周比较,造模1周表达明显,且雌鼠优于雄鼠;恢复1个月后,各组大鼠的表达较1周和2周造模时期下降。结论:5%盐酸普萘洛尔乳膏剂诱导银屑病样大鼠模型,重复性好,与造模2周相比造模1周效果好,雌鼠优于雄鼠,高剂量造模效果更好。Objective:To study the effect of 5%propranolol hydrochloride cream on the modeling effect of psoriasis-like rats at different doses,times,and sexes.Methods:The rats were randomly divided into 6 groups:female blank,high(2.7 g/4 cm^(2))and low(1.2 g/4 cm^(2))dose groups;male blank,high(2.7 g/4 cm^(2))and low(1.2 g/4 cm^(2))dose groups;and the 5%propranolol hydrochloride cream agent was uniformly applied to the skin of the backs of the rats once a day for 1 week and 2 weeks,respectively,to set up a 1-month recovery period.By comparing the psoriasis area and severity index(psoriasis area and severity index,PASI),HE staining,and immunohistochemistry to detect proliferating cell nuclear antigen(proliferating cell nuclear antigen,PCNA)and cytokeratin(CK-17),ELISA and RT-qPCR for inflammatory cytokine expression in rats,we could evaluate the severity of skin lesions and the effect of modeling.Results:Compared with the blank group,rats in the high and low dose groups of both sexes at 1 and 2 weeks of modeling showed obvious erythema,scaling and hypertrophy,hyperkeratosis,thickening of the epidermis,increased expression of PCNA and CK-17,and elevated expression of IL-1β,IL-17A,IL-22,IL-23,and TNF-αin serum and lesions;compared with the 2-week modeling period,the expression was obvious in the 1-week period of modeling,and female rats were better than male rats;after 1 month of recovery,the expression of rats in all groups decreased compared with the 1-week and 2-week modeling periods.Conclusion:The induction of a psoriasis-like rat model by 5%propranolol hydrochloride cream was reproducible,and the effect of 1 week of modeling was better than that of 2 weeks of modeling.Female rats were better than male rats,and the effect of modeling was better at high doses.

关 键 词：盐酸普萘洛尔 银屑病样大鼠模型 造模药剂量 造模时间 

分 类 号：R758.63[医药卫生—皮肤病学与性病学] R-332[医药卫生—临床医学]