Effect of topical nitric oxide donors on epidermal hyperplasia in mice with impaired barrier function / 中华皮肤科杂志

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.