Effect of dexmedetomidine pretreatment on MIRI in rats and its mechanism

YANG Xueer; WU Mingxiao; ZHANG Chaofan; JIA Junwen; HU Chunyang; WEN Linyong; LI Gang; JIN Lianjin

doi:10.3969/j.issn.1002-266X.2023.29.009

Abstract：Objective To investigate the protective effect of dexmedetomidine(Dex)pretreatment on myocardial ischemia-reperfusion injury(MIRI)rats and to explore whether its mechanism was related to oxidative stress and Epac1/Rap1 signaling pathway.Methods SD rats were randomly divided into the sham operation group,model group,Dex group and inhibitor group,with 8 rats in each.Rats in the Dex group were intraperitoneally injected with dexmedetomidine 30 min before modeling.In the inhibitor group,Epac1 antagonists ESI09 and Dex were intraperitoneally injected 30 min and 25 min before modeling.Rats in the sham operation group and model group were intraperitoneally injected with the same dose of normal saline 30 min before modeling.Except the sham operation group,MIRI models were established by li-gation of the left coronary artery in other groups.In the sham operation group,the heart was only threaded without ligation of the left coronary artery.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial tis-sues.ELISA was used to detect creatine kinase-MB(CK-MB),lactate dehydrogenase(LDH),malondialdehyde(MDA)and superoxide dismutase(SOD).The expression levels of Epac1 and Rap1 signaling pathway-related proteins in the rat myocardial tissues were detected by Western blotting.Results In the sham operation group,the myocardial fibers were arranged neatly,the edges were clear,and there was no myocardial fiber rupture and intercellular swelling;in the model group,the myocardial fibers showed rupture,disordered arrangement,fuzzy boundary,obvious neutrophil infiltration,and obvious intercellular swelling;in the Dex group and inhibitor group,myocardial fiber rupture,neutrophil infiltration and interstitial swelling were reduced.Serum CK-MB was as follows:LDH model group>Dex group>inhibitor group>sham operation group,the serum MDA was in the following order:model group>Dex group>inhibitor group>sham opera-tion group,serum SOD was as follows:sham operation group>inhibitor group>Dex group>model group,and the expres-sion levels of Epac1 and Rap1 proteins in the myocardial tissues were as follows:model group>Dex group>inhibitor group>sham operation group(all P<0.05).Conclusion Dex preconditioning has a protective effect on myocardial I/R injury rats,and the mechanism may be related to activating Epac1/Rap1 signaling pathway to reduce oxidative stress in the myocardial tissues.