Antioxidant system in photoaged skin of hairless mouse

无毛小鼠光老化皮肤的抗氧化系统

• 批准号: 11670836
• 负责人: SHIMIZU Kazuhiro
• 金额: $ 1.15万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670836/
• 关键词: photoaging; hairless mouse; UVA; SOD; MMP; solar elastosis; tropoelastin; 光老化; ヘアレスマウス; 紫外線

The cutaneous change of photoaging is caused by long-term repetitive photo-irradiation and "solar elastosis" is observed in the dermis. UV irradiation is the representative of oxidative stress and long-term repetitive irradiation is the repeat of oxidative stress. The chronic exposure to UV ray is harmful to the skin which can cause oxidative damage, and the change of antioxidant system would affect the other signal transduction system, especially through the redox regulation system. To clarify the mechanism of long-term repetitive UVA (300-420nm) irradiation in photoaged skin, we evaluated albino hairless mice by repetitive UVA irradiation for 12 months. The mice were divided into 7 groups of five individuals. Three groups were irradiated for 5 days per week for 4, 8 and 12 months. The other 3 groups were treated as age-matched controls. Mice in the irradiated groups received a daily dose of 30 J/cm^2/day. For this purpose, we established an animal model to analyze the cutaneous photoaging in human. The dorsal skins of mice were taken from each group and applied to immunohistochemistry, zymography, RT-PCR and culture. The analysis of tropoelastin, matrix metalloproteinase (MMP) 2 and MMP9 was performed and the expression of MMP9 mRNA was found to be significantly increased in cultured fibroblast derived from irradiated mice at 12 month. In zymograph, MMP9 activity was higher in irradiated group than that in non-irradiated group. These results suggest that MMP9 is an important mediator in the development of UVA irradiated skin for one-year. The existence of cutaneous photoaging means the accumulation of chronic UV exposure which can influence the antioxidant system. Next, we performed the quantitative analysis of the expression of superoxide dismutase in the transcription level, which was the representative enzyme of antioxidant system and scavenged O^-_2.

光老化的皮肤变化是由长期重复的光照射引起的，在真皮中观察到“太阳弹性”。紫外线照射是氧化应激的代表，长期重复照射是氧化应激的重复。长期暴露在紫外线下对皮肤有害，可引起氧化损伤，而抗氧化系统的改变会影响其他信号转导系统，特别是通过氧化还原调节系统。为了阐明长期重复UVA （300-420nm）照射对光老化皮肤的作用机制，我们对白化病无毛小鼠进行了12个月的重复UVA照射。这些老鼠被分成7组，每组5只。三组每周照射5天，连续照射4、8、12个月。另外3组作为年龄匹配的对照组。辐照组小鼠的日剂量为30 J/cm^2/天。为此，我们建立了动物模型来分析人体皮肤光老化。取各组小鼠背部皮肤进行免疫组织化学、酶谱、RT-PCR和培养。对辐照后小鼠成纤维细胞进行对抗性弹性蛋白、基质金属蛋白酶（MMP） 2和MMP9的分析，发现MMP9 mRNA的表达在12月龄时显著升高。酶谱图显示，辐照组MMP9活性明显高于未辐照组。这些结果表明，MMP9是UVA照射一年皮肤发育的重要介质。皮肤光老化的存在是指长期暴露在紫外线下而影响抗氧化系统的积累。接下来，我们在转录水平上定量分析了超氧化物歧化酶的表达，它是抗氧化系统的代表酶，清除O^-_2。

项目成果

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Bae Sang Jae, et al: "Autocrine induction of substance P mRNA and peptide in cultured normal human keratinocytes."Biochem Biophys Res Commun. 263-2. 327-333 (1999)

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