Effects of κ-opioid receptor agonist U50448H on pyroptosis and NLRP3 of lung in rats with cardiopulmonary bypass

Li Long; Gao Guangjie

doi:10.13498/j.cnki.chin.j.ecc.2024.04.12

Abstract：Objective To explore the potential protective mechanism of κ-opioid receptor agonist U50488H in acute lung injury(ALI)induced by cardiopulmonary bypass(CPB)through observing its effects on NLRP3 inflammasome and pyroptosis in lung tissues of rats undergoing CPB.Methods 24 adult male SD rats weighing 350-450 g,were randomly divided into three groups:sham operation group(sham group),CPB group,CPB+KORs agonist group(U50488H group).U50488H 1.5 mg/kg was intravenously injected 30 minutes before CPB in group U50488H.Arterial blood gas analysis was performed at 0 h,1 h,and 2 h after CPB,and the alveolar-arterial oxygen difference(AaDO2)and respiratory index(RI)were calculated.All rats in the three groups were sacrificed 2 hours after wean off CPB.The intact right lower lobe of the lung was taken,and the extravascular lung water(EVLW)was measured by the gravimetric method.HE staining was used to observe the morphological changes of lung tissue.ELISA was applied to test the level of LPS,TNF-α,IL-6 and IL-4 in serum.Western blot was performed for examining the expression of GSDMD-C,GSDMD-N,NLRP3 and pro-Caspase-1 in lung tissue.Results The values of AaDO2,RI and LPS at 0 h,1 h and 2 h after CPB in CPB group were higher than those in sham group(P<0.05),while the values of AaDO2,RI and LPS in U50488H group were significantly lower than those in CPB group(P<0.05).Compared with the sham group,the levels of EVLW,plasma TNF-α,IL-6 and lung GSDMD-C,GSDMD-N,NLRP3,pro-Caspase-1 were increased,and the levels of plasma IL-4 was decreased in CPB group,which were statistically significant(P<0.05),while the above indexes were not significantly different in U50488H group(P>0.05).The rats of CPB group performed serious lung damage,intra-alveolar congestion/hemorrhage and massive inflammatory cell infiltration.The lung injury was alleviated in U50448H group.Conclusion The KOR agonist U50488H inhibits NLRP3 inflammasome-induced pyroptosis during ALI induced by CPB,thereby mitigating post-CPB lung injury.