Cardioprotective Effect On The Myocardial Ischemia-reperfusion Injury By Lycopuslucidus Turcz Of Traditional Chinese Korean Medicine Via PI3K/Akt/mTOR Signaling Pathway In Rats

Objective:To explore the cardioprotective effects on myocardial ischemia and reperfusion(I/R)by ethanol extract of Lycopus Lycidus Turcz(ELT)in an isolated perfused rat heart by PI3K/Akt/mTOR signaling pathway.Methods:96 healthy male SD rats(weight 200±20 g)were fed for 7 days and randomly divided into 8 groups:normal group(Control),model group(I/R),high dose group of ELT(ELTH),low dose group of ELT(ELTL),high dose group of BA(BAH),low dose group of BA(BAL),high dose group of RA(RAH),low dose group of RA(RAL).There were 12 rats in each group.After each SD rat broke the cervical vertebra,the heart was removed and hung on the Langendorff instrument:(1)In the normal group,perfusion with K-H buffer for 120 minutes;(2)In the model group,after perfusion with K-H buffer solution for 40 minutes,the whole heart was stopped for 20 minutes and then reperfused for 60 minutes;(3)In the administration group,the K-H buffer solution was perfused for 20 minutes,then the administration was performed for 20 minutes,and the whole heart was stopped for 20 minutes,followed by 60 minutes of perfusion.Use Powerlab physiological recorder to record and compare hemodynamic data between groups;TTC staining was used to detect the area of myocardial infarction;Use ELISA kit to detect the changes of CK-MB,SOD,LDH,cTn-T in tissues;Observe the structural changes of myocardial tissue by HE staining;Observe the apoptosis rate by TUNEL staining;The unilateral expressions of PI3K,p-PI3K,Akt,p-Akt,mTOR,p-mTOR and HIF-lαin cardiomyocytes were measured by WesternBlot method.Result:The ELT and its active components significantly improved the level of LVSP,+dp/dt max,LVEDP,-dp/dt min,LVDP,RPP(P<0.05);The ELT and its active components also reduced the release of CK,cTn-T and LDH caused by myocardial ischemia-reperfusion injury and increased the release of SOD(P<0.05)from myocardial tissue(P<0.05);HE staining showed that ELT and its active components significantly improved myocardial fiber arrangement and nuclear integrity(P<0.05);Cardiomyocytes apoptosis rate by TUNEL showed that ELT and its active components were more able to reduce the cardiomyocytes apoptosis rate compared to the model group of myocardial ischemia-reperfusion injury(P<0.05);Western blotting showed that compared with ischemic and reperfusion model group,the protein levels of HIF-1α in the ELT and its active components treatment groups were decreased significantly,while the levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR were increased significantly(P<0.05).Conclusion:ELT and its active components improved myocardial ischemia reperfused injury in the isolated perfused rat hearts,and its mechanism might be associated with PI3K/Akt/mTOR signaling pathway.