Protective effect of usnic acid on myocardial ischemia-reperfusion injury in rats by regulating the cGAS-STING signaling pathway
Objective To investigate the protective effect of usnic acid on myocardial ischemia-reperfusion injury(MIRI)in rats by regulating the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods Fifty healthy Sprague-Dawley(SD)rats were selected and randomly grouped into sham operation group,model group,low-dose usnic acid group(25mg/kg),high-dose usnic acid group(100mg/kg),and RU.521 group(cGAS inhibitor,5mg/kg),with 10 rats per group.A rat MIRI model was established by ligating the left anterior descending coronary artery and reperfusion.The hematoxylin and eosin(H&E)staining was applied to observe the pathological changes in rat myocardial tissues.The terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)was applied to detect cardiomyocyte apoptosis.Nitro Blue Tetrazolium(NBT)staining was applied to detect the percentage of myocardial infarction area.Commercial kits were applied to detect the levels of superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)in myocardial tissues.Serum levels of creatine kinase MB(CK-MB),tumor necrosis factor-alpha(TNF-α),and interleukin 6(IL-6)were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expressions of cGAS and STING in myocardial tissues were detected by real-time reverse transcription polymerase chain reaction(RT-PCR).Protein expressions of Bax,Bcl-2,Caspase-3,cGAS and STING were detected by Western blot.Results In the sham operation group,the myocardial tissue morphology was normal and the apoptosis rate was low.Compared with those of the sham operation group,rats in the model group presented severely damaged myocardial cells,significantly increased apoptosis rate,the percentage of myocardial infarction area,serum levels of CK-MB,TNF-α and IL-6,MDA,mRNA levels of cGAS and STING,and protein levels of Bax,Caspase-3,cGAS,and STING,and significantly decreased SOD and CAT levels,and the protein level of Bcl-2(P<0.05).Compared with those of the model group,rats in the low-dose and high-dose usnic acid group and RU.521 group presented improved morphology and structure of myocardial cells,significantly reduced infiltration of inflammatory cells,significantly decreased apoptosis rate,the percentage of myocardial infarction area,serum levels of CK-MB,TNF-α and IL-6,MDA,mRNA levels of cGAS and STING,and protein levels of Bax,Caspase-3,cGAS,and STING,and significantly increased SOD and CAT levels,and the protein level of Bcl-2(P<0.05).The above indexes were comparable between RU.521 group and high-dose usnic acid group.Conclusion Usnic acid has a protective effect on MIRI in rats by inhibiting the cGAS-STING signaling pathway.
usnic acidcyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathwaymyocardial ischemia reperfusionapoptosis
万方数据
维普
