SUBSTANCE-P AND NITRIC-OXIDE MEDIATE WOUND-HEALING OF ULTRAVIOLET PHOTODAMAGED RAT SKIN - EVIDENCE FOR AN EFFECT OF NITRIC-OXIDE ON KERATINOCYTE PROLIFERATION
SUBSTANCE-P AND NITRIC-OXIDE MEDIATE WOUND-HEALING OF ULTRAVIOLET PHOTODAMAGED RAT SKIN - EVIDENCE FOR AN EFFECT OF NITRIC-OXIDE ON KERATINOCYTE PROLIFERATION
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DOI：
10.1016/0304-3940(95)12062-9
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发表时间：
1995-11-10
影响因子：
2.5
通讯作者：
GILLARDON, F
中科院分区：
文献类型：
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作者：
BENRATH, J;ZIMMERMAN, M;GILLARDON, F
由于最近已证明神经肽参与体内伤口愈合，我们通过局部施用特定拮抗剂研究了 P 物质 (SP)、降钙素基因相关肽 (CGRP) 和一氧化氮 (NO) 在紫外线 (UV) 光损伤大鼠皮肤再生中的作用。局部应用神经激肽 (NK)(1)-受体拮抗剂 (2S,3S)-cis-2-(二苯基甲基)-N-[(2-甲氧基苯基)甲基]-1-氮杂双环[2.2.2]辛烷-3-胺 (CP-96,345) 显着延迟紫外线照射后所有时间点坏死面积的减少，而局部施用 NO 合酶抑制剂N-G-硝基-L-精氨酸甲酯盐酸盐 (L-NAME) 仅在照射后 7 天导致坏死面积增加。更重要的是，局部施用 L-NAME 而不是 SP 降低了紫外线暴露表皮的增殖细胞核抗原 (PCNA) 的核免疫标记，表明 NO 介导的角质形成细胞增殖刺激。这些发现表明，内源性 SP 和 NO 在紫外线引起的皮肤损伤后伤口愈合中具有营养功能，这可能是通过刺激血管生成或表皮细胞增殖来介导的。
Since it has been demonstrated recently that neuropeptides are involved in wound healing in vivo we investigated the role of substance P (SP), calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in regeneration of ultraviolet (UV) photodamaged rat skin by topical administration of specific antagonists. topical application of the neurokinin (NK)(1)-receptor antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine (CP-96,345) significantly delayed the reduction of the necrotic area at all timepoints post UV-irradiation, whereas topically administered NO synthase inhibitor N-G-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in an increased necrotic area only at 7 days post-irradiation. More important, topically administered L-NAME but not SP reduced nuclear immunolabelling for proliferating cell nuclear antigen (PCNA) of the UV-exposed epidermis, suggesting a NO-mediated stimulation of keratinocyte proliferation. These findings suggest that endogenous SP and NO have a trophic function in wound healing after UV-induced damage of the skin which may be mediated by stimulation of angiogenesis or epidermal cell proliferation.