Improvement effects of astragaloside Ⅳ on myocardial focal ischemia-reperfusion inj ury and its influence in PI3K/Akt/mTOR signaling pathway / 吉林大学学报(医学版)

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 inj ury 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 inj ury were randomly divided into model group (normal saline), AS-Ⅳ group (intravenous inj ection of 10 mg·kg-1 AS-Ⅳ 5 min before reperfusion),PI3K inhibitor Wortmannin (WOR)group (intravenous injection of 0.6 mg·kg-1 WOR 10 min before reperfusion)and AS-Ⅳ+WOR group (intravenous injection of 10 mg·kg-1 AS-Ⅳ and 0.6 mg·kg-1 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 ej ection 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.