Rutin alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

被引:14
作者
Chen, Shengsong [1 ,2 ,3 ,4 ,5 ,6 ]
Bai, Yu [1 ,2 ,3 ,4 ,5 ,6 ]
Xia, Jingen [1 ,3 ,4 ,5 ,6 ]
Zhang, Yi [1 ,3 ,4 ,5 ,6 ]
Zhan, Qingyuan [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] China Japan Friendship Hosp, Ctr Resp Med, Dept Pulm & Crit Care Med, 2 East Yinghua Rd, Beijing 100029, Peoples R China
[2] Chinese Acad Med Sci, Peking Union Med Coll, 9 Dongdan Santiao, Beijing 100730, Peoples R China
[3] Natl Ctr Resp Med, 2 East Yinghua Rd, Beijing 100029, Peoples R China
[4] Chinese Acad Med Sci, Inst Resp Med, 2 East Yinghua Rd, Beijing 100029, Peoples R China
[5] Natl Clin Res Ctr Resp Dis, 2 East Yinghua Rd, Beijing 100029, Peoples R China
[6] WHO Collaborating Ctr Tobacco Cessat & Resp Dis P, 2 East Yinghua Rd, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
OXIDATIVE STRESS; LIPOPOLYSACCHARIDE; MACROPHAGES; CONTRIBUTES; MICE;
D O I
10.1016/j.isci.2023.107866
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Whether rutin relieves ventilator-induced lung injury (VILI) remains unclear. Here, we used network pharmacology, bioinformatics, and molecular docking to predict the therapeutic targets and potential mechanisms of rutin in the treatment of VILI. Subsequently, a mouse model of VILI was established to confirm the effects of rutin on VILI. HE staining showed that rutin alleviated VILI. TUNEL staining showed that rutin reduced apoptosis in the lung tissue of mice with VILI, and the same change was observed in the ratio of Bax/Bcl2. Furthermore, rutin reduced the expression of NLRP3, ASC, Caspase1, IL1 beta, and IL18 in the lung tissues of mice with VILI. Mechanistically, rutin suppressed the TLR4/NF-kappa B-P65 pathway, which promoted the M1 to M2 macrophage transition and alleviated inflammation in mice with VILI. Rutin relieved NLRP3 inflammasome activation by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NF-kappa B-P65 pathway, resulting in the amelioration of VILI in mice.
引用
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页数:17
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