急性臭氧暴露诱导心肌损伤的作用及其机制OA

OBJECTIVE To investigate myocardial injury and mechanisms of acute ozone(O3)exposure.METHODS Eight-week-old male C57BL/6J mice were divided into a control group and three O3-exposed groups at concentrations of 0.25,0.50 and 1.00 ppm,with 10 mice in each group.Mice in exposure groups were dynamically exposed to O3 for 6 hours per day for 7 days while the control mice inhaled filtered air.Body weight was recorded after the final exposure.Myocardial pathological changes were evaluated using HE staining,and serum cardiac troponin T(cTnT)levels were measured by ELISA.Proteomic analysis was conducted to identify differentially expressed proteins in myocardial tissues and to perform enrichment analyses.Western blotting was used to detect the protein expressions of hypoxia-inducible factor-1α(HIF-1α),heme oxygenase-1(HO-1),ferritin heavy chain(FTH),ferritin light chain(FTL),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in mouse heart tissues.RESULTS Compared with the control group,inflammatory cell infil-tration of varying degrees in the myocardium was observed in O3-exposed mice in the 1.00 ppm O3 group,myocardial fiber was disorganized,serum cTnT levels significantly elevated and body weight decreased.Proteomic analysis found that the myocardial protein expression profile in the 1.00 ppm O3 group was significantly altered compared to the control group.Specifically,a total of 565 differentially expressed proteins were identified,including 340 up-regulated and 225 down-regulated ones,which were primarily enriched in such pathways as complement and coagulation cascades,hypoxic response,and ferroptosis.Western blotting showed that HIF-1α and HO-1 protein expression levels were signifi-cantly elevated in the 1.00 ppm O3 group compared with the control group.Moreover,in each of O3 con-centration groups,expression levels of FTL,FTH,and ACSL4 were significantly elevated,while the GPX4 expression was significantly decreased.CONCLUSION Acute O3 exposure can induce myocar-dial injury in mice,and the underlying toxicological mechanism is associated with the increase of HIF-1α expression and ferroptosis.