Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
Int Immunopharmacol. 2021 Jul;96:107600. doi: 10.1016/j.intimp.2021.107600. Epub 2021 Mar 30.
Inflammation plays a major role in the pathogenesis of acute lung injury (ALI), but the mechanism remains unclear. Current anti-inflammatory therapy has poor efficacy on ALI. The aim of this study was to investigate the protective mechanism of curcumin against ALI. In in vivo experiments, curcumin significantly alleviated lung inflammation, histopathological injury and MPO activity, serum concentrations of CCL7, IL-6 and TNF-α, and mortality in mice compared to the model group. RAW264.7 cells cultured in the presence of lipopolysaccharide and adenosine triphosphate showed significantly lower viability, higher pyroptotic percentage and inflammation, but supplement of curcumin increased the cell viability, reduced pyroptosis and inflammation. Additionally, the expressions of NF-κB and pyroptosis related proteins were notably increased, while Sirtuin 1 (SIRT1) was decreased in both in vivo and in vitro ALI models. The results suggested that curcumin remarkably inhibited the expression of NF-κB and pyroptosis related proteins and increased the expression of SIRT1. However, EX527, a SIRT1 inhibitor, blocked the protective effect of curcumin against ALI. In conclusion, curcumin has protective effect against ALI. It may inhibit inflammatory process by inhibiting the activation of NLRP3 inflammasome-dependent pyroptosis through the up-regulation of SIRT1.
炎症在急性肺损伤(ALI)的发病机制中起主要作用,但机制尚不清楚。目前的抗炎治疗对 ALI 疗效不佳。本研究旨在探讨姜黄素对 ALI 的保护机制。在体内实验中,与模型组相比,姜黄素显著减轻了小鼠的肺炎症、组织病理学损伤和 MPO 活性、血清 CCL7、IL-6 和 TNF-α浓度以及死亡率。在脂多糖和三磷酸腺苷存在下培养的 RAW264.7 细胞活力明显降低,细胞焦亡比例和炎症明显升高,但姜黄素的补充增加了细胞活力,减少了细胞焦亡和炎症。此外,NF-κB 和细胞焦亡相关蛋白的表达在体内和体外 ALI 模型中均明显增加,而 Sirtuin 1(SIRT1)的表达在两种模型中均降低。结果表明,姜黄素显著抑制 NF-κB 和细胞焦亡相关蛋白的表达,增加 SIRT1 的表达。然而,SIRT1 抑制剂 EX527 阻断了姜黄素对 ALI 的保护作用。总之,姜黄素对 ALI 具有保护作用。它可能通过上调 SIRT1 抑制 NLRP3 炎性小体依赖性细胞焦亡来抑制炎症过程。