Resveratrol attenuates sepsis-induced lung injury by suppressing NLRP3-mediated pyroptosis
Yu-Ting Li, Xiao-Qi Yue, Jun-Chao Liu, Si-Han You, Jing Wang, Miao Jiang, Shao-Xuan Wang, Zhen-Ao Zhao, Chun-Yu Niu, Zi-Gang ZhaoBackground:
Sepsis-induced acute lung injury (ALI) is a severe condition with a high mortality rate and limited treatment options. Although NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome-mediated pyroptosis is a key driver of ALI, the role of the natural anti-inflammatory polyphenol resveratrol (RSV) in this specific pathway remains unclear. Therefore, this study investigated the role of NLRP3-mediated pyroptosis in septic ALI and evaluated the therapeutic potential of RSV.
Methods:
A murine sepsis model was established by intraperitoneal injection of allogeneic fecal filtrate (FF) and RSV (30 mg/kg) was administered intramuscularly. Survival rates, Murine Sepsis Score (MSS), lung histopathology, wet-to-dry ratio, lung function, protein levels of pyroptosis-related markers (NLRP3, ASC, Caspase-1, GSDMD, IL-1β, IL-18), and barrier markers (E-cadherin and VE-cadherin) were measured. Subsequently, the effect of
Results:
Sepsis-induced severe lung injury was characterized by elevated MSS, impaired lung function, increased pyroptosis-related protein expression, and decreased barrier-related protein expression. RSV treatment significantly improved survival rates, attenuated lung injury and pyroptosis, and restored the lung barrier function. Similar protective effects were observed in
Conclusion:
RSV alleviated sepsis-induced lung injury by inhibiting NLRP3-mediated pyroptosis and preserving pulmonary barrier integrity.