Resveratrol protects against CIH-induced myocardial injury by targeting Nrf2 and blocking NLRP3 inflammasome activation

Life Sci. 2020 Mar 15:245:117362. doi: 10.1016/j.lfs.2020.117362. Epub 2020 Jan 27.

Abstract

The prominent feature of obstructive sleep apnea (OSA) is chronic intermittent hypoxia (CIH). Given the strong antioxidant ability of resveratrol against oxidative stress, we evaluated the potential protective effects of resveratrol on myocardial injury induced by CIH. Twenty-four rats were divided into normal control group, CIH group, CIH plus resveratrol treated (CIH + Res) group, and resveratrol treated control (Res) group. We proved that CIH impaired cardiac structure and function with an increase in oxidative stress, endoplasmic reticulum (ER) stress and NOD-like receptors (NLRP3) inflammasome induction in heart, which was attenuated after resveratrol administration. NLRP3 inflammasome blockade by resveratrol appeared to be mediated by activating AMP-activated Protein Kinase (AMPK), which could restrain mTOR/TTP/NLRP3 mRNA signalling. Furthermore, resveratrol attenuated CIH-induced oxidative stress through elevation antioxidant molecules expression via NF-E2-related factor-2 (Nrf2). Moreover, AMPK may play a role in Nrf2/HO-1 signalling by resveratrol. These results expand our understanding of the myocardial protective mechanism of resveratrol during CIH and suggest that resveratrol treatment may be useful to counteract OSA-associated cardiac injury.

Keywords: Chronic intermittent hypoxia; Heart; NLRP3; Nrf2; Resveratrol.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Blotting, Western
  • Echocardiography
  • Fluorescent Antibody Technique
  • Hypoxia / complications*
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Male
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / pathology
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*

Substances

  • Antioxidants
  • Inflammasomes
  • NF-E2-Related Factor 2
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nfe2l2 protein, rat
  • Nlrp3 protein, rat
  • Resveratrol