HO-1通过BV-BVR-TJ途径修复皮肤屏障在特应性皮炎中的作用研究

氧化应激是引起特应性皮炎（AD）皮肤屏障功能障碍及免疫异常的重要因素。HO-1及其酶促产物胆绿素（BV）具有强大的抗氧化及抗炎等细胞保护作用。应用外源性HO-1能减轻AD皮损但机制不清。我们的前期结果表明外源性BV通过激活BV还原酶（BVR）抑制紫外线引起的炎症并修复皮肤屏障。HO-1通过BV-BVR途径是调控TJ蛋白表达，修复皮肤屏障，还是抑制炎症反应而在AD中具有保护作用，抑或兼而有之是本研究亟待阐明的问题。本研究拟首先分析内源性HO-1及BV在AD患者中的代谢水平及它们与AD严重程度的关系；其次通过动物实验，利用基因敲除等技术，明确外源性HO-1及BV对AD的保护作用；通过细胞实验，阐明HO-1-BV-BVR途径通过调控TLR4/NF-KB及PI3K/Art通路而影响TJ蛋白及炎症因子表达的分子机制。本研究首次探讨HO-1-BV-BVR对AD的影响，为探索新的治疗靶点奠定理论基础。

Oxidative stress is an important factor in skin barrier dysfunction and immune abnormalities in atopic dermatitis (AD). Heme oxygenase 1 (HO-1) and its product bilverdin (BV) are important endogenous antioxidants in the body, with strong antioxidant and anti-inflammatory cytokines. The study found that the application of HO-1 can improve the AD lesions, but the mechanism is unknown. Our previous results showed that exogenous BV inhibits UV-induced inflammation and repairs the skin barrier by activating BV reductase (BVR). Whether HO-1 and its product BV have a protective effect in AD by regulating the expression of skin barrier-associated proteins or by inhibiting the immune inflammatory reaction, or both, is an issue to be elucidated in this study. This study intends to analyze the metabolic levels of HO-1 and BV in AD patients and their relationship with the severity of AD ；To determine the protective effect of exogenous HO-1 and BV on AD through in vivo experiments； And by using biological techniques including gene knockout through cell experiments, to elucidate the molecular mechanisms underlying the HO-1-BV-BVR pathway affecting the expression of TJ protein and inflammatory cytokines through the regulation of key pathways TLR4/NF-KB and PI3K/Art. This study first explores the impact of HO-1-BV-BVR on AD, and lays a theoretical foundation for exploring new therapeutic targets.