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

Shengsong Chen; Yu Bai; Jingen Xia; Yi Zhang; Qingyuan Zhan

doi:10.1016/j.isci.2023.107866

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

iScience. 2023 Sep 9;26(10):107866. doi: 10.1016/j.isci.2023.107866. eCollection 2023 Oct 20.

Authors

Shengsong Chen^{1

2

3

4

5

6}, Yu Bai^{1

2

3

4

5

6}, Jingen Xia^{1

3

4

5

6}, Yi Zhang^{1

3

4

5

6}, Qingyuan Zhan^{1

2

3

4

5

6}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P.R.China.
² Peking Union Medical College, Chinese Academy of Medical Sciences, No 9 Dongdan Santiao, Dongcheng District, Beijing 100730, P.R.China.
³ National Center for Respiratory Medicine, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P.R.China.
⁴ Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P.R.China.
⁵ National Clinical Research Center for Respiratory Diseases, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P.R.China.
⁶ WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P.R.China.

Abstract

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, IL1β, and IL18 in the lung tissues of mice with VILI. Mechanistically, rutin suppressed the TLR4/NF-κB-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-κB-P65 pathway, resulting in the amelioration of VILI in mice.

Keywords: Cell biology; Immunology; Molecular biology.