Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
The Key Hepatosplenic Surgery Laboratory, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Biomed Pharmacother. 2016 Dec;84:130-138. doi: 10.1016/j.biopha.2016.09.020. Epub 2016 Sep 16.
NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI. Resveratrol treatment alleviated the LPS-induced lung pathological damage, lung edema and neutrophil infiltration. In addition, resveratrol reversed the LPS-mediated elevation of IL-1β and IL-18 level in the BAL fluids. In lung tissue, resveratrol also inhibited the LPS-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-κB p65 nuclear translocation, NF-κB activity and ROS production in the LPS-treated mice, but also inhibited the LPS-induced thioredoxin-interacting protein (TXNIP) protein expression and interaction of TXNIP-NLRP3 in lung tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the LPS-challenged mice. Taken together, our study suggests that resveratrol protects against LPS-induced lung injury by NLRP3 inflammasome inhibition. These findings further suggest that resveratrol may be of great value in the treatment of ALI and a potential and an effective pharmacological agent for inflammasome-relevant diseases.
NLRP3 炎性小体在急性肺损伤 (ALI) 的发展中起着关键作用，加速了 IL-1β 和 IL-18 的释放并诱导了肺部炎症。白藜芦醇是一种天然植物抗毒素，具有抗炎特性，可通过抑制氧化、白细胞致敏和炎症介质的产生来实现。在这项研究中，我们旨在研究白藜芦醇对脂多糖诱导的 ALI 中 NLRP3 炎性小体的影响。通过气管内滴注 3mg/kg 脂多糖 (LPS) 来诱导 ALI。白藜芦醇治疗减轻了 LPS 诱导的肺病理损伤、肺水肿和中性粒细胞浸润。此外，白藜芦醇逆转了 LPS 介导的 BAL 液中 IL-1β 和 IL-18 水平的升高。在肺组织中，白藜芦醇还抑制了 LPS 诱导的 NLRP3、ASC、半胱天冬酶-1 mRNA 和蛋白表达以及 NLRP3 炎性小体的激活。此外，白藜芦醇给药不仅抑制了 LPS 处理的小鼠中 NF-κB p65 核易位、NF-κB 活性和 ROS 产生，还抑制了 LPS 诱导的 TXNIP 蛋白表达和 TXNIP-NLRP3 在肺组织中的相互作用。同时，白藜芦醇在 LPS 刺激的小鼠中明显诱导了 SIRT1 mRNA 和蛋白表达。综上所述，我们的研究表明，白藜芦醇通过抑制 NLRP3 炎性小体来保护 LPS 诱导的肺损伤。这些发现进一步表明，白藜芦醇在 ALI 的治疗中具有很高的价值，并且是一种潜在的、有效的炎症小体相关疾病的药理学药物。
