水母雪莲多糖减轻中波紫外线引起皮肤光老化作用及分子机制研究

The residents of the Tibetan Plateau have been exposure to strong ultraviolet radiation over a long period of time. Long time excessive radiation has caused premature photoaging and related disease. The existing research confirmed that ultraviolet (UVB) irradiation targets keratinocytes (keratinocyte, KC).Our previous results showed that polysaccharides of Saussurea medusa Maxim. can reduce oxidative damage and apoptosis, obviously recover the shape of HaCaT cell via a P38MAPK-independent mechanism. Therefore, we proposed that polysaccharides of Saussurea medusa Maxim. may exhibit protective role during phototaging process caused by ultraviolet (UVB) irradiation through other pathway. Thereby, we propose that: 1、the establishment of photoaging model in vivo and in vitro (subcutaneous injection of D-galactose combined with UVB irradiation),different doses of polysaccharide of Saussurea medusa Maxim. intervention observe its effects of skin aging model;2、 by detecting the expressions of ERK and MMPs proteins and the level of key molecules in the pathway of oxygen free radical scavenging , primarily clarifying the molecular mechanism of polysaccharide of Saussurea medusa Maxim. during protective role for photoaging caused by UVB. This project could provide new ideas and theoretical basis for the treatment of skin lesions disease caused by high altitude due to UVB in Platean area.

青藏高原地区居住人群长期暴露于强紫外线中，可导致皮肤提前光老化及罹患相关疾病。现有研究证实：中波紫外线（UVB）靶向作用于角质形成细胞（keratinocyte，KC）。本项目组前期研究发现，水母雪莲（Saussurea medusa Maxim.）多糖能够通过不依赖P38-MAPK通路机制途径减轻细胞凋亡及氧化损伤，明显恢复中波紫外线（UVB）辐射后角质形成细胞的形态。据此我们推测：水母雪莲多糖可能通过其它通路对中波紫外线引起的皮肤光老化具有一定的保护作用。故本项目拟：1、通过UVB辐射与D-半乳糖皮下注射方法建立的皮肤老化体内外研究模型，用水母雪莲多糖干预，观察其对皮肤衰老模型的影响；2、通过检测ERK-MMPs、氧自由基清除相关途径关键分子水平变化，阐明水母雪莲多糖减轻皮肤光老化作用的分子机制。本研究将为高原地区UVB引起的皮肤损伤疾病治疗提供新思路和理论依据。

青藏高原地区平均海拔4000m以上，是全国太阳辐射量最多的地区。光损伤性皮肤病特别是皮肤光老化发病率高。紫外线辐射是致皮肤老化或皮肤癌发展最重要的环境因素。课题组前期实验证实水母雪莲多糖能够通过减轻细胞凋亡减轻UVB辐射HaCaT细胞后的氧化损伤，且发现水母雪莲多糖对于中波紫外线引起的小鼠皮肤光老化具有保护作用。本课题旨在探讨水母雪莲多糖能否减轻中波紫外线诱导的皮肤光老化及其作用机制，为临床应用提供理论基础。通过建立体内外皮肤光老化模型，以低剂量水母雪莲多糖和高剂量水母雪莲多糖作为干预因素，通过试剂盒（SOD、MDA、ROS 试剂盒）检测各项生化指标，并通过 Western blot 和免疫荧光检测 EGFR、ERK 及 MMP等的表达，发现模型组EGFR、MEK、ERK1/2、c-fos、c-jun、MMP-1蛋白的表达高于对照组（P<0.05），VE组、低剂量水母雪莲给药组及高剂量水母雪莲给药组EGFR、MEK、ERK1/2、c-fos、c-jun、MMP-1蛋白的表达低于模型组（P<0.05），其中高剂量水母雪莲给药组较VE组、低剂量水母雪莲给药组变化最为明显（P<0.05）证明水母雪莲多糖能通过ERK/MMP-1通路减轻UVB诱导的皮肤光老化损伤，为临床治疗皮肤光老化和相关产品研发提供新思路。