局部外用一氧化氮供体对屏障功能破坏的小鼠表皮增生的影响  

Effect of topical nitric oxide donors on epidermal hyperplasia in mice with impaired barrier function

作　　者：孙梦珂 文思 张书常 郭盼 王晓华 胡立志 Sun Mengke;Wen Si;Zhang Shuchang;Guo Pan;Wang Xiaohua;Hu Lizhi(Department of Pathogen Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300052,China;Pharmaceutical Preparation Center,Dermatology Hospital of Southern Medical University,Guangzhou 510091,China;Department of Immunology,Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),Tianjin Medical University,Tianjin 300052,China)

机构地区：[1]天津医科大学基础医学院病原生物学系,300052 [2]南方医科大学皮肤病医院制剂中心,广州510091 [3]天津医科大学免疫微环境与疾病省部共建教育部重点实验室,300052

出　　处：《中华皮肤科杂志》2021年第7期620-624,共5页Chinese Journal of Dermatology

基　　金：国家自然科学基金(81573075、81972962)。

摘　　要：目的探讨一氧化氮(NO)对屏障功能破坏的小鼠表皮增生的影响。方法将15只SKH1无毛小鼠按随机数字表法分为正常对照组(3只)、S-亚硝基-N-乙酰青霉胺(SNAP)处理组(4只)、屏障破坏组(4只)、屏障破坏+SNAP处理组(4只);将15只C57BL/6J小鼠随机分为正常对照组、屏障破坏组、屏障破坏+硝普钠(SNP)处理组,每组5只。正常对照组小鼠背部涂抹丙二醇-乙醇混合溶剂;SNAP处理组仅涂抹SNAP溶液;屏障破坏组采用胶带反复粘贴背部皮肤并涂抹丙二醇-乙醇混合溶剂,每天2次;屏障破坏+SNAP或SNP处理组小鼠经胶带处理后涂抹10 mmol/L SNAP或SNP溶液。各组均连续处理4 d,第5天处死小鼠并取皮肤组织,制作石蜡切片,苏木精-伊红(HE)染色,检测表皮厚度,增殖细胞核抗原(PCNA)染色检测表皮增殖细胞。多组间比较采用双因素方差分析和单因素方差分析,两组间多重比较采用LSD-t检验。结果SNAP处理组SKH1小鼠表皮厚度及PCNA阳性细胞数与正常对照组相比差异均无统计学意义(t值分别为0.33、1.25,P值分别为0.748、0.246)。与正常对照组相比,屏障破坏组SKH1和C57BL/6J小鼠表皮厚度均明显增加,PCNA阳性细胞数均明显增多(均P<0.01)。屏障破坏组SKH1小鼠表皮厚度为(50.4±5.4)μm,PCNA阳性细胞数为(87.3±3.8)个/mm,而C57BL/6J小鼠分别为(45.9±3.7)μm和(232.0±19.3)个/mm,与之相比,屏障破坏+SNAP处理组SKH1小鼠及C57BL/6J小鼠表皮均显著增厚[(127.5±12.0)μm,(78.1±7.6)μm,均P<0.001],且PCNA阳性细胞数均明显增多[(120.0±5.0)个/mm,(285.0±15.0)个/mm,均P<0.01]。结论局部NO供体处理不影响正常表皮增生,但在表皮屏障功能破坏状态下,NO供体促进表皮增生,提示皮肤状态影响局部NO供体对表皮增生的作用。Objective To evaluate the effect of nitric oxide on epidermal hyperplasia in mice with impaired barrier function.Methods Fifteen SKH1 hairless mice were divided into 4 groups by using a random number table:normal control group(3 mice),S-nitroso-N-acetyl-DL-penicillamine(SNAP)group(4 mice),barrier-impaired group(4 mice),SNAP-treated barrier-impaired group(4 mice).Fifteen C57BL/6J mice were randomly and equally divided into 3 groups:normal control group,barrier-impaired group and sodium nitroprusside(SNP)-treated barrier-impaired group.Mice in the two normal control groups were both topically treated with propylene glycol-ethanol mixtures on the back;those in the SNAP group were topically treated with SNAP solution alone;those in the two barrier-impaired groups were both treated with repeated tape peeling followed by topical application of propylene glycol-ethanol mixtures on the back twice a day;those in the SNAP-or SNP-treated barrier-impaired group were treated with repeated tape peeling followed by topical application of 10-mmol/L SNAP or SNP solution on the back twice a day.After 4 consecutive days of treatment,all the mice were sacrificed on day 5,and skin tissues were resected from the back of mice followed by preparation of paraffin sections.Hematoxylin-eosin(HE)staining was performed to measure the epidermal thickness,and proliferating cell nuclear antigen(PCNA)staining was conducted to detect proliferating cells in the epidermis.Two-way analysis of variance and one-way analysis of variance were used for comparisons among groups,and least significant difference-t test was used for multiple comparisons.Results No significant difference in the epidermal thickness or number of PCNA-positive cells was observed between the SNAP group and normal control group(t=0.33,1.25,P=0.748,0.246,respectively).Compared with the corresponding normal control groups,the barrier-impaired groups showed significantly increased epidermal thickness and number of PCNA-positive cells(all P<0.01).Compared with the corresponding barrie

关 键 词：一氧化氮 一氧化氮供体 表皮 增生 细胞增殖 屏障功能 

分 类 号：R965[医药卫生—药理学]