受体相互作用蛋白1在紫外线诱导人皮肤成纤维细胞坏死性凋亡中的作用及机制研究

Receptor Interacting Protein 1(RIP1) is an important cell signal transduction molecules which is also the key and essential protein to necroptosis. The present studies show necroposis plays an important role in various physiological conditions and diseases which is mediated by RIP1. The expression and function of RIP1 were poorly understood in photodamage. Our previous proteomics study firstly discovered that RIP1 was significantly increased by ultraviolet in the human dermal fibroblasts which was also confirmed by Western Blot. Based on our previous results, the scientific hypothesis has been put forward：Necroptosis was involved in photodamage of fibroblasts which was mediated by RIP1 and related signaling molecules . A variety of experimental methods such as Real time PCR，Western blot was employed to investigate the effect and mechanism of RIP1 in necroptosis of fibroblasts induced by ultraviolet. This project is the extension and expansion of creative found, is expected to obtain further original achievement.

受体相互作用蛋白1(RIP1)是一种重要的细胞信号转导分子，是细胞发生坏死性凋亡的关键蛋白和必需蛋白，其介导的坏死性凋亡参与了多种疾病的发生发展，但中波紫外线损伤人皮肤成纤维细胞中RIP1的表达与功能知之甚少。我们前期蛋白质组学及Western Blot的研究首次发现紫外线照射人皮肤成纤维细胞后RIP1表达明显升高，且预实验结果显示抑制RIP1可以减少紫外线诱导的成纤维细胞的坏死。为此，我们提出假说：RIP1及相关信号分子介导的坏死性凋亡参与了紫外线损伤人皮肤成纤维细胞的机制。为证实此假说，我们将通过原代人皮肤成纤维细胞紫外线损伤模型，采用Real time PCR、Western Blot、RNA干扰等成熟手段研究RIP1在紫外线损伤人皮肤成纤维细胞中的作用，明确RIP1及相关信号分子介导的坏死性凋亡是否参与了紫外线对人皮肤成纤维细胞的损伤，为紫外线损伤的防治提供新的研究思路。

受体相互作用蛋白1(RIP1)是一种重要的细胞信号转导分子，是细胞发生坏死性凋亡的关键蛋白和必需蛋白，其介导的坏死性凋亡参与了多种疾病的发生发展，但中波紫外线损伤人皮肤成纤维细胞中RIP1的表达与功能知之甚少。我们前期蛋白质组学及Western Blot的研究首次发现紫外线照射人皮肤成纤维细胞后RIP1表达明显升高，且预实验结果显示抑制RIP1可以减少紫外线诱导的成纤维细胞的坏死。为此，我们提出假说：RIP1及相关信号分子介导的坏死性凋亡参与了紫外线损伤人皮肤成纤维细胞的机制。为证实此假说，我们将通过原代人皮肤成纤维细胞紫外线损伤模型，采用Real time PCR、Western Blot、RNA干扰等成熟手段研究RIP1在紫外线损伤人皮肤成纤维细胞中的作用。研究发现，发现UVB照射可以诱导人皮肤成纤维细胞发生坏死性凋亡，分别干扰及抑制RIP1、RIP3的表达后，UVB照射成纤维细胞诱导的坏死性凋亡会明显下降，RIP1及RIP3参与了UVB照射诱导的人皮肤成纤维细胞的坏死性凋亡，RIP1及RIP3干扰后活性氧的产生会明显减少，抑制Caspase-8或抑制ROS后成纤维细胞凋亡减少，坏死表现增多，因此，RIP1可能通过与RIP3相互作用影响下游活性氧的产生进而参与到紫外线损伤中，本研究从坏死性凋亡这个新思路揭示 UVB 对成纤维细胞损伤的机制，为紫外线的防护提供新的研究基础。