| ObjectiveThis study was established a rat model of myocardial ischemia-reperfusion injury(MIRI)to explore the effects of rosmarinic acid on myocardial cell apoptosis and myocardial tissue injury by regulating PI3K/Akt signaling pathway,and to provide some reference for clinical drug treatment of MIRI.Methods40 healthy SD rats were randomly divided into sham operation group,model group,rosmarinic acid group and rosmarinic acid + inhibitor group,with10 rats in each group.Early MIRI rat models were established in the other three groups except the sham operation group.5 min before reperfusion,the model group was injected with normal saline,the rosmarinic acid group was injected with 30 mg/kg rosmarinic acid,and the rosmarinic acid + inhibitor group was injected with 30 mg/kg rosmarinic acid and 0.3 mg/kg LY294002.2 h after reperfusion,the pathological changes of myocardial tissue were observed by HE staining,myocardial injury markers of creatine kinase(CK),creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI),lactate dehydrogenase(LDH)and oxidative stress indicators of superoxide dismutase(SOD),malondialdehyde(MDA)were detected by Elisa,protein expressions of PI3 K,p-PI3 K,Akt and p-Akt were detected by Western blot,apoptosis index was detected by Tunel assay,protein expressions of Bax and Bcl-2 were detected by immunohistochemistry.Results1.HE staining showed that myocardial cells in the rosmarinic acid group were arranged more neatly,with fewer vacuoles,a few inflammatory cells infiltrated,and the nuclear staining depth was more uniform.Compared with the rosmarinic acid group,the myocardial cells were disordered,with more vacuoles,more inflammatory cell infiltration and uneven nuclear staining depthin the rosmarinic acid +inhibitor group.2.The levels of SOD in sham operation group,rosmarinic acid group and rosmarinic acid + inhibitor group were significantly higher than those in model group,and the levels of SOD in rosmarinic acid + inhibitor group were significantly lower than those in rosmarinic acid group(P<0.05).The levels of MDA in sham operation group,rosmarinic acid group and rosmarinic acid +inhibitor group were significantly lower than those in model group,and the levels of MDA in rosmarinic acid + inhibitor group were significantly higher than those in rosmarinic acid group(P<0.05).3.The levels of CK,CK-MB,cTnI and LDH in sham operation group,rosmarinic acid group and rosmarinic acid + inhibitor group were significantly lower than those in model group,and the above myocardial injury markers in rosmarinic acid + inhibitor group were significantly higher than those in rosmarinic acid group(P<0.05).4.The apoptosis index in sham operation group,rosmarinic acid group and rosmarinic acid + inhibitor group were significantly lower than those in model group,while the apoptosis index in rosmarinic acid+inhibitor group were significantly higher than those in rosmarinic acid group(P<0.05).5.The protein expressions in myocardial tissue of Bax in sham operation group,rosmarinic acid group and rosmarinic acid + inhibitor group were significantly lower than those in model group,while the protein expressions of Bax in rosmarinic acid + inhibitor group were significantly higher than those in rosmarinic acid group(P<0.05).The protein expressions in myocardial tissue of Bcl-2 in sham operation group,rosmarinic acid group and rosmarinic acid +inhibitor group were significantly higher than those in model group,while the protein expressions of Bcl-2 in rosmarinic acid + inhibitor group were significantly lower than those in rosmarinic acid group(P<0.05).6.The protein expressions in myocardial tissue of PI3 K,p-PI3 K,Akt and p-Akt in sham operation group,rosmarinic acid group and rosmarinic acid +inhibitor group were significantly higher than those in model group,while the above protein expressions in rosmarinic acid + inhibitor group were significantly lower than those in rosmarinic acid group(P<0.05).Conclusions1.This study was established a rat model of MIRI,to confirm that rosmarinic acid could regulate the protein expressions of Bax and Bcl-2 by participating in PI3K/Akt signaling pathway,and inhibit the apoptosis of cardiomyocytes.2.Rosmarinic acid could inhibit oxidative stress response,reduce myocardial cell damage and protect myocardial tissue in MIRI rats.3.Rosmarinic acid could be expressed through PI3K/Akt signaling pathway and had protective effect on myocardial cells in MIRI rat model. |
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