Xu Wenxia, Ou Dingqin, Zhao Yufei, Liu Yuan, Yan Peng, Li Shuang, Sun Qimao, Zhang Xiong, Liu Hong, Huang Jie, Fang Yu
Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming 650500, Yunnan, China.
Department of Anesthesiology, West China Second University Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Cell Signal. 2025 Oct;134:111909. doi: 10.1016/j.cellsig.2025.111909. Epub 2025 May 27.
The glycocalyx, a cell surface component implicated in various diseases, has recently been recognized for its role in acute lung injury (ALI). Also known as the alveolar epithelial polysaccharide coat, it is vital for maintaining lung barrier integrity, fluid homeostasis, and defense against pathogens. This study investigated the protective effects and mechanisms of curcumin, a natural polyphenol, against lipopolysaccharide (LPS) -induced alveolar epithelial glycocalyx damage. Key findings include: in vitro pretreatment with 20 μM curcumin for 2 h before a 24-h exposure to 10 μg/mL LPS markedly reduced heparan sulfate (HS) degradation by regulating heparanase (HPSE) expression. Mechanistic studies demonstrated that curcumin suppressed LPS-induced Ras-related C3 botulinum toxin substrate 1 (Rac1) expression and downstream nuclear factor kappa B (NF-κB) pathway activation, while upregulation of Rac1 protein abolished its protective effects. Furthermore, in vivo, administration of 200 mg/kg curcumin significantly reduced lung inflammation induced by 5 mg/kg LPS in mice. This treatment enhanced alveolar-capillary barrier function, evidenced by reduced levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-α), and HPSE. Curcumin also reduced damage to HS and syndecan-1 (SDC-1), a crucial component of the glycocalyx. This study is the first to indicate that curcumin protects against LPS-induced lung injury by reducing damage to the alveolar epithelial glycocalyx by inhibiting the Rac1/NF-κB/HPSE pathway.
糖萼是一种与多种疾病相关的细胞表面成分，最近其在急性肺损伤（ALI）中的作用得到了认可。它也被称为肺泡上皮多糖包被，对于维持肺屏障完整性、液体稳态以及抵御病原体至关重要。本研究调查了天然多酚姜黄素对脂多糖（LPS）诱导的肺泡上皮糖萼损伤的保护作用及其机制。主要发现包括：在体外，在暴露于10μg/mL LPS 24小时之前，用20μM姜黄素预处理2小时可通过调节乙酰肝素酶（HPSE）的表达显著减少硫酸乙酰肝素（HS）的降解。机制研究表明，姜黄素抑制LPS诱导的Ras相关C3肉毒杆菌毒素底物1（Rac1）表达和下游核因子κB（NF-κB）途径的激活，而Rac1蛋白的上调则消除了其保护作用。此外，在体内，给予200mg/kg姜黄素可显著减轻5mg/kg LPS诱导的小鼠肺部炎症。这种治疗增强了肺泡-毛细血管屏障功能，白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子-α（TNF-α）和HPSE水平降低证明了这一点。姜黄素还减少了对HS和糖萼的关键成分syndecan-1（SDC-1）的损伤。本研究首次表明，姜黄素通过抑制Rac1/NF-κB/HPSE途径减少对肺泡上皮糖萼的损伤，从而预防LPS诱导的肺损伤。
