Lopes Fernanda Barbosa, Sarandy Mariáurea Matias, Novaes Rômulo Dias, Valacchi Giuseppe, Gonçalves Reggiani Vilela
Department of General Biology, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
Plants for Human Health Institute, Animal Science Department, North Carolina State University, North Carolina Research Campus, Kannapolis, NC 28081, USA.
Antioxidants (Basel). 2024 Jul 9;13(7):823. doi: 10.3390/antiox13070823.
Significant sums are spent every year to find effective treatments to control inflammation and speed up the repair of damaged skin. This study investigated the main mechanisms involved in the skin wound cure. Consequently, it offered guidance to develop new therapies to control OxInflammation and infection and decrease functional loss and cost issues. This systematic review was conducted using the PRISMA guidelines, with a structured search in the MEDLINE (PubMed), Scopus, and Web of Science databases, analyzing 23 original studies. Bias analysis and study quality were assessed using the SYRCLE tool (Prospero number is CRD262 936). Our results highlight the activation of membrane receptors (IFN-δ, TNF-α, toll-like) in phagocytes, especially macrophages, during early wound healing. The STAT1, IP3, and NF-kβ pathways are positively regulated, while Ca mobilization correlates with ROS production and NLRP3 inflammasome activation. This pathway activation leads to the proteolytic cleavage of caspase-1, releasing IL-1β and IL-18, which are responsible for immune modulation and vasodilation. Mediators such as IL-1, iNOS, TNF-α, and TGF-β are released, influencing pro- and anti-inflammatory cascades, increasing ROS levels, and inducing the oxidation of lipids, proteins, and DNA. During healing, the respiratory burst depletes antioxidant defenses (SOD, CAT, GST), creating a pro-oxidative environment. The IFN-δ pathway, ROS production, and inflammatory markers establish a positive feedback loop, recruiting more polymorphonuclear cells and reinforcing the positive interaction between oxidative stress and inflammation. This process is crucial because, in the immune system, the vicious positive cycle between ROS, the oxidative environment, and, above all, the activation of the NLRP3 inflammasome inappropriately triggers hypoxia, increases ROS levels, activates pro-inflammatory cytokines and inhibits the antioxidant action and resolution of anti-inflammatory cytokines, contributing to the evolution of chronic inflammation and tissue damage.
每年都要花费大量资金来寻找有效的治疗方法，以控制炎症并加速受损皮肤的修复。本研究调查了皮肤伤口愈合所涉及的主要机制。因此，它为开发控制氧化炎症和感染、减少功能丧失和成本问题的新疗法提供了指导。本系统评价按照PRISMA指南进行，在MEDLINE（PubMed）、Scopus和Web of Science数据库中进行结构化检索，分析了23项原始研究。使用SYRCLE工具（Prospero编号为CRD262 936）评估偏倚分析和研究质量。我们的结果强调了在伤口愈合早期，吞噬细胞尤其是巨噬细胞中膜受体（IFN-δ、TNF-α、Toll样受体）的激活。STAT1、IP3和NF-kβ通路被正向调节，而钙动员与活性氧生成和NLRP3炎性小体激活相关。这种通路激活导致caspase-1的蛋白水解切割，释放IL-1β和IL-18，它们负责免疫调节和血管舒张。诸如IL-1、诱导型一氧化氮合酶、TNF-α和转化生长因子-β等介质被释放，影响促炎和抗炎级联反应，增加活性氧水平，并诱导脂质、蛋白质和DNA的氧化。在愈合过程中，呼吸爆发消耗了抗氧化防御物质（超氧化物歧化酶、过氧化氢酶、谷胱甘肽S-转移酶），营造了一个促氧化环境。IFN-δ通路、活性氧生成和炎症标志物建立了一个正反馈回路，招募更多的多形核细胞，并加强氧化应激与炎症之间的正向相互作用。这个过程至关重要，因为在免疫系统中，活性氧、氧化环境，尤其是NLRP3炎性小体的激活之间的恶性正循环会不适当地引发缺氧，增加活性氧水平，激活促炎细胞因子并抑制抗炎细胞因子的抗氧化作用和消退，从而导致慢性炎症和组织损伤的发展。
