Sulforaphane Alleviates Postresuscitation Lung Pyroptosis Possibly via Activating the Nrf2/Ho-1 Pathway

Abstract

Introduction Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion following cardiac arrest and resuscitation. Methods After animal preparation, twenty-four pigs were randomly divided into Sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 ml of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase (SOD), the contents of malondialdehyde (MDA), interleukin-1β (IL-1β), and interleukin-18 (IL-18), and the expression levels of NOD-like receptor pyrin domain 3 (NLRP3), cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal (GSDMD-N), Nrf2, and HO-1. Results During CPR, spontaneous circulation was achieved in 6 and 7 pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and OI) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (SOD, MDA), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis-related proteins (NLRP3, cleaved caspase 1, GSDMD, GSDMD-N), and activated the Nrf2/HO-1 pathway when compared to the CPR group. Conclusions SFN produced effective post-resuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.