Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5555310 | International Immunopharmacology | 2017 | 8 Pages |
â¢Resveratrol treatment alleviates cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome activationâ¢Resveratrol suppresses NLRP3 inflammasome activation by increasing autophagy activityâ¢Sirt1 plays a vital role in resveratrol-mediated enhancement of autophagy activityâ¢Sirt1-dependent autophagy activity is critical for resveratrol-mediated inhibition of NLRP3 inflammasome activation
Resveratrol has been reported to protect against cerebral ischemia/reperfusion (I/R) injury in rats, but the underlying mechanism is unclear. In the current study, we examined whether resveratrol ameliorates cerebral I/R injury by inhibiting NLRP3 inflammasome-derived inflammation and whether autophagy is involved in this process. In addition, we explored the role of Sirt1 in resveratrol-mediated protective effects.To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 1 h followed by 24 h reperfusion.We found that cerebral I/R increased levels of activated NLRP3 inflammasome, caspase-1, IL-1β, and IL-18 and enhanced autophagy activity (ratio of LC3B-II/LC3B-I and p62/SQSTM1). Treatment with resveratrol, a specific Sirt1 agonist, attenuated I/R-induced NLRP3 inflammasome-derived inflammation but upregulated autophagy. Furthermore, resveratrol treatment clearly reduced cerebral infarct volume, decreased brain water content, and improved neurological scores. In addition, inhibition of autophagy using 3-MA intracerebroventricular injection blocked the inhibitory effect of resveratrol on NLRP3 inflammasome activation. Finally, Sirt1 knockdown with siRNA significantly blocked resveratrol-induced enhancement of autophagy activity and suppression of NLRP3 inflammasome activation.In conclusion, our results demonstrate that resveratrol protects against cerebral I/R injury by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy activity.