1. Academic Validation
  2. Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

  • BMC Anesthesiol. 2022 Dec 1;22(1):369. doi: 10.1186/s12871-022-01874-4.
Mengjie Liu # 1 2 Yaqiang Zhang # 3 Jie Yan 2 Yuelan Wang 4 5 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Perioperative Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, 250012, Jinan, Shandong, China.
  • 2 Department of Anesthesiology and Perioperative Medicine, Shandong Institute of Anesthesia and Respiratory Intensive Care Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, China.
  • 3 Beijing Sport University, Xinxi Road, Haidian District, 100084, Beijing, China.
  • 4 Department of Anesthesiology and Perioperative Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, 250012, Jinan, Shandong, China. wyldgf@163.com.
  • 5 Department of Anesthesiology and Perioperative Medicine, Shandong Institute of Anesthesia and Respiratory Intensive Care Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, China. wyldgf@163.com.
  • 6 Department of Anesthesiology and Perioperative Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, 250014, Jinan, China. wyldgf@163.com.
  • # Contributed equally.
Abstract

Background: Ventilator-induced lung injury (VILI) is caused by stretch stimulation and other factors related to mechanical ventilation (MV). NOD-like receptor protein 3 (NLRP3), an important innate immune component, is strongly associated with VILI. This study aimed to investigate the effect and mechanisms of aerobic exercise (EX) on VILI.

Methods: To test the effects of the PKC Inhibitor bisindolylmaleimide I on PKC and NLRP3, male C57BL/6 mice (7 weeks old, 19 ~ 23 g) were randomly divided into four groups: control group(C), bisindolylmaleimide I-pretreated group(B), MV group, and bisindolylmaleimide I-pretreated + MV (B + MV) group. The mice were pretreated with bisindolylmaleimide I through intraperitoneal injection (0.02 mg/kg) 1 h before MV. MV was performed at a high tidal volume (30 ml/kg). To explore the ameliorative effect of EX on VILI, the mice were randomly divided into C group, MV group, EX group and EX + MV group and subjected to either MV or 5 weeks of EX training. After ventilation, haematoxylin-eosin (HE) staining and wet/dry weight ratio was used to assess lung pathophysiological changes. PKCɑ, P-PKCɑ, ASC, procaspase-1, Caspase-1, pro-IL-1β, IL-1β, NLRP3 and occludin (tight junction protein) expression in lung tissues was determined by Western blotting. The level of IL-6 in alveolar lavage fluid was determined by ELISA.

Results: NLRP3, P-PKCɑ, and PKCɑ levels were inceased in MV group, but bisindolylmaleimide I treatment reversed these changes. Inhibition of PKC production prevented NLRP3 activation. Moreover, MV increased ASC, procaspase-1, Caspase-1, pro-IL-1β, and IL1β levels and decreased occludin levels, but EX alleviated these changes. HE staining and lung injury scoring confirmed an absence of obvious lung injury in C group and EX group. Lung injury was most severe in MV group but was improved in EX + MV group. Overall, these findings suggest that MV activates the NLRP3 inflammasome by activating PKCɑ and inducing occludin degradation, while Exercise attenuates NLRP3 inflammasome and PKCɑ activation. Besides, exercise improves cyclic stretch-induced degradation of occludin.

Conclusion: PKC activation can increase the level of NLRP3, which can lead to lung injury. Exercise can reduce lung injury by inhibiting PKCɑ and NLRP3 activation. Exercise maybe a potential measure for clinical prevention of VILI.

Keywords

Aerobic exercise; NLRP3 inflammasome; Ventilator-induced lung injury.

Figures
Products