Maslinic acid alleviates myocardial ischemia/reperfusion injury by inhibiting pyroptosis / 中华老年心脑血管病杂志

ABSTRACT

Objective To investigate the mechanism of maslinic acid on pyroptosis and inflammato-ry response in myocardial ischemia/reperfusion(IR)injury.Methods H9C2 cardiomyocytes were randomly divided into control group,control+maslinic acid group,hypoxia reoxygenation(HR)group,and HR+maslinic acid group.Cellular model of HR injury was constructed by hypoxia for 4 h and then reoxygenation for 12 h.Forty-eight male SD rats were randomly divided into Sham group,IR group,IR+maslinic acid group,IR+maslinic acid+Tri group(n=12).Rat model of myocardial IR injury was established by ligating the left anterior descending branch for 30 min followed by reperfusion for 2 h.The viability of cardiomyocytes was detected,the levels of LDH,CK-MB,IL-1β and IL-18 in the supernatant of cardiomyocytes and rat serum samples were detec-ted in each group.Drug-molecular docking was performed to predict the binding site and binding force of maslinic acid and NOD-like receptor thermal protein domain-associated protein 3(NLRP3).Western blotting was used to detect IκBα,NF-κB P65,NLRP3,apoptosis-associated speck-like protein(ASC),and gasdermid D-N terminal(GSDMD-N)in each group of cardiomyo-cytes and myocardial tissues.Results Compared with the Control group,significantly reduced cell viability,enhanced protein levels of p-IκBα,p-NF-κB P65 and higher releases of LDH,IL-1β and IL-18 were observed in the HR group(P＜0.05).Maslinic acid treatment reversed HR-induced changes in above indicators(P＜0.05).Compared with the Sham group,the protein levels of p-IκBα,p-NF-κB P65,NLRP3,ASC,GSDMD-N and the releases of serum CK-MB,LDH,IL-1βand IL-18 were significantly increased in the IR group(P＜0.05).Maslinic acid treatment also reversed above indicators induced by IR injury(P＜0.05).The protein levels of p-IκBα,p-NF-κB P65,NLRP3,ASC and GSDMD-N were significantly increased,and the releases of serum CK-MB,LDH,IL-1β and IL-18 were also elevated in the IR+maslinic acid+Tri group than the IR+maslinic acid group(1681.00±136.20 U/L vs 1251.00±213.60 U/L,1776.00±185.80 U/L vs 1330.00±172.50 U/L,4.32±0.45 vs 2.95±0.26,3.89±0.20 vs 2.47±0.29,P＜0.05).Conclusion Maslinic acid can show target intervention in NLRP3 activity,thereby inhibiting inflammatory re-sponse and cell pyroptosis,and ultimately attenuate myocardial IR injury effectively.