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红景天苷预处理通过调节 NLRP3 炎性小体抑制细胞凋亡和焦亡缓解 PM 所致肺损伤。

Salidroside pretreatment alleviates PM caused lung injury via inhibition of apoptosis and pyroptosis through regulating NLRP3 Inflammasome.

机构信息

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, 4123, Switzerland; Faculty of Science, University of Basel, Basel, 4058, Switzerland.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.

出版信息

Food Chem Toxicol. 2023 Jul;177:113858. doi: 10.1016/j.fct.2023.113858. Epub 2023 May 24.

DOI:10.1016/j.fct.2023.113858
PMID:37236293
Abstract

Ambient fine particulate matter (PM) is considered a leading cause of pathogenic particulate matter induced lung injury. And Salidroside (Sal), the major bioactive constituent isolated from Rhodiola rosea L., has been shown to ameliorate lung injury in various conditions. To uncover the possible therapy for PM related pulmonary disease, we evaluated the protective role of Sal pre-treatment on PM induced lung injury in mice by utilizing the survival analysis, hematoxylin and eosin (H&E) staining, lung injury score, lung wet-to-dry weight ratio, enzyme-linked immunosorbent assay (ELISA) kits, immunoblot, immunofluorescence, and transmission electron microscopy (TEM). Impressively, our findings strongly indicated Sal as an effective precaution against PM induced lung injury. Pre-administration of Sal before PM treatment reduced the mortality within 120 h and alleviated inflammatory responses by reducing the release of proinflammatory cytokines, including TNF-α, IL-1β, and IL-18. Meanwhile, Sal pretreatment blocked apoptosis and pyroptosis that introduced the tissue damage under PM treatment via regulating Bax/Bcl-2/caspase-3 and NF-κB/NLRP3/caspase-1 signal pathways. In summary, our research demonstrated that Sal could be a potential preventative therapy for PM caused lung injury by inhibiting the initiation and development of apoptosis and pyroptosis through down-regulating NLRP3 inflammasome pathway.

摘要

环境细颗粒物 (PM) 被认为是导致致病颗粒物质引起肺损伤的主要原因。而从红景天中分离得到的主要生物活性成分红景天苷 (Sal) 已被证明可改善各种情况下的肺损伤。为了揭示 PM 相关肺部疾病的可能治疗方法,我们通过生存分析、苏木精和伊红 (H&E) 染色、肺损伤评分、肺湿重/干重比、酶联免疫吸附测定 (ELISA) 试剂盒、免疫印迹、免疫荧光和透射电子显微镜 (TEM) 评估了 Sal 预处理对 PM 诱导的小鼠肺损伤的保护作用。令人印象深刻的是,我们的研究结果强烈表明 Sal 是一种预防 PM 诱导肺损伤的有效药物。在 PM 治疗前给予 Sal 预处理可降低 120 小时内的死亡率,并通过减少促炎细胞因子(包括 TNF-α、IL-1β 和 IL-18)的释放来减轻炎症反应。同时,Sal 预处理通过调节 Bax/Bcl-2/caspase-3 和 NF-κB/NLRP3/caspase-1 信号通路阻断了 PM 处理下引入组织损伤的细胞凋亡和细胞焦亡。总之,我们的研究表明,Sal 可通过下调 NLRP3 炎性小体途径抑制细胞凋亡和细胞焦亡的发生和发展,成为 PM 引起的肺损伤的一种潜在预防治疗方法。

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