| Objective:The incidence of atrial fibrillation increased after cardiac surgery,which is related to inflammation.However,the specific mechanism is still unclear.Our previous study found that the expression of TRPV4 channel in the atrium of rats increased after sterile pericarditis(SP),and the blocking of TRPV4 channel significantly reduced the atrial fibrillation induction in SP rats.This study aimed to investigate whether TRPV4 is involved in the occurrence of POAF by activating NLRP3 inflammasomes using a mouse SP model.The purpose of this study was to investigate whether TRPV4 is involved in the occurrence of POAF by activating NLRP3 inflammasomes in a mouse SP model.Methods: Sterile talcum powder were spread evenly on the atrium surface of mice to establish a mouse SP model.Atrial tissues were collected at different time points(8 h,12 h,24 h,48 h,and 72 h)after operation,Western blot was used to detect NLRP3 inflammasomes(NLRP3,ASC,Caspase-1-P20,and Caspase-1-P45),inflammatory factors(IL-1β,TNF-α,IL-6),and activation of NF-κb / P65,MAPK / ERK signaling pathway.Mice were given TRPV4 channel-specific agonist GSK1016790 A or TRPV4 channel specific blocker GSK2193874 before operation in mice.At 48 hours after surgery,electrophysiological catheters were used to programmatically stimulate atrial fibrillation in the right atrium of Sham group,SP group,Vehicle group,GSK2193874 group,and TRPV4-/-group,respectively.The atrial fibrillation induction rate was recorded.Results: Compared with the sham group,the rate of atrial fibrillation induction was significantly increased after SP in mice,and the rate of AF induction was significantly reduced after TRPV4 gene knockout.Compared with Vehicle group,GSK2193874 treatment significantly reduced atrial fibrillation induction rate after SP.NLRP3 in the atrial tissue of mice began to increase 24 hours after SP,and ASC,Caspase-1-P20,IL-1β,TNF-α,IL-6 began to increase at 12 hours after SP,and NF-κb / P65 and MAPK/ERK phosphorylation levels also began to increase at 12 h after SP,while Caspase-1-P45 expression increased only at 72 h after SP.GSK1016790 A treatment can further increase the expression of NLRP3,ASC,Caspase-1-P20,IL-1β,TNF-α,IL-6 and the activation of NF-κb / P65 and MAPK / ERK signaling pathways after SP;GSK2193874 treatment can significantly reverse SPinduced increase in NLRP3,ASC,Caspase-1-P20,IL-1β,TNF-α,IL-6 expression and activation of NF-κB / P65,MAPK / ERK signaling pathway.Conclusion: Atrial fibrillation increased after SP in mice.One of the mechanisms may be that the TRPV4 channel activates NF-κb / P65 and MAPK / ERK signaling pathways to activate the NLRP3 inflammasome and mediate the occurrence and development of POAF. |
