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

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（SN...

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

【Abstract】 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 barrier-impaired groups, SNAP -treated barrier-impaired group and SNP-treated barrier-impaired group both showed significantly increased epidermal thickness （SKH1: 127.5 ± 12.0 μm vs. 50.4 ± 5.4 μm; C57BL/6J: 78.1 ± 7.6 μm vs. 45.9 ± 3.7 μm; both P < 0.001） and number of PCNA-positive cells （SKH1: 120.0 ± 5.0 cells/mm vs. 87.3 ± 3.8 cells/mm; C57BL/6J: 285.0 ± 15.0 cells/mm vs. 232.0 ± 19.3 cells/mm; both P < 0.01）. Conclusion Topical nitric oxide donors did not affect normal epidermis, but could aggravate epidermal hyperplasia in barrier-impaired skin, suggesting that skin condition affects the effect of topical nitric oxide donors on epidermal hyperplasia.