Abstract: 【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.

Key words: Nitric oxide, Nitric oxide donors, Epidermis, Hyperplasia, Cell proliferation, Barrier function