Abstract:

Abstract:Objective To observe the improvement effects of astragaloside Ⅳ (AS-Ⅳ) on the myocardial focal ischemia-reperfusion (I/R) injury and its influence in PI3K/Akt/mTOR pathway,and to clarify the protective effect of AS-Ⅳ on myocardial I/R injury and the possible mechanisms.Methods The left main coronary arteries of 60 Sprague-Dawley rats  were occluded for 30 min followed by a 120-min reperfusion to induce I/R model.The rats with I/R injury were randomly divided into model group (normal saline),AS-Ⅳ group (intravenous injection of 10 mg/kg AS-Ⅳ 5 min before reperfusion),PI3K inhibitor Wortmannin (WOR) group (intravenous injection of 0.6 mg/kg WOR 10 min before reperfusion) and AS-Ⅳ+WOR group (intravenous injection of   10 mg/kg AS-Ⅳ and 0.6 mg/kg WOR  5 and 10 min before reperfusion,respectively).15 age-matched SD rats were chosen as control group.The heart  mass,degrees of infarction and ischemia and cardiac function ,including left ventricular systolic mean pressure (LVSP),end-diastolic pressure (LVEDP),fractional shortening (FS) and ejection fraction (EF), of the rats in all groups were analyzed.Western blotting method was used to measure the phosphorylation levels of Akt and mTOR(p-Akt and p-mTOR).The specific fluorescent probe DHE staining was employed to detect the myocardial reactive oxygen species levels.Results Compared with control group,the degrees of infarction and ischemia,LVEDP,myocardial levels of p-Akt/Akt,p-mTOR/mTOR and reactive oxygen species levels of the rats were increased (P<0.05). and the levels of LVSP,FS and EF were decreased in model group (P<0.05). Compared with the model group,the degrees of infarction and ischemia,LVEDP and reactive oxygen species level were decreased (P<0.05),while the levels of p-Akt/Akt,p-mTOR/mTOR LVSP,FS and EF of all rats in AS-Ⅳ group were increased (P<0.05).Compared with AS-Ⅳ group,the degrees of infarction and ischemia,LVEDP and reactive oxygen species levels of the rats in   WOR group and AS-Ⅳ+WOR group were increased(P<0.05),and the myocardial  p-Akt/Akt,p-mTOR/mTOR and  LVSP,FS,EF were decreased (P<0.05).Conclusion AS-Ⅳ has improvement effect on myocardial I/R injury.AS-Ⅳ can reduce the extent of myocardial infarction and oxidative stress and improve the heart function,and its possible mechanism may be related to activating PI3K/Akt/mTOR signaling pathway.

Key words: astragaloside Ⅳ, myocardial ischemia-reperfusion injury, PI3K/Akt/mTOR pathway