Olprinone alleviates myocardial ischemia/reperfusion injury via regulating autophagy in rats / 中华急诊医学杂志

ABSTRACT

Objective To observe the effects of olprinone on ischemia/reperfusion (I/R) induced myocardial injury in male (Sprague-Dawley, SD rats) and explore its mechanisms. Methods Rats were subjected to a 30-min coronary arterial occlusion followed by 24-hour reperfusion. The survival rats were randomly divided into sham group (n=6), ischemia reperfusion group (I/R group, n=9), ischemia reperfusion+low dose of olprinone group(IR+olprinone-L group, n=6), ischemia reperfusion+medium dose of olprinone group (IR+olprinone-M group, n=6),ischemia reperfusion +high dose of olprinone group (IR+olprinone-H group, n=6). A MAP heart function analysis system was used to measure hemodynamic parameters; TTC staining method was used to detect the myocardial infarct size;24-hour mortality of SD rats was recorded; western blot was used to detect the levels of Caspase-3, Bax,Bcl-2, LC3B/LC3A,Beclin-1. Results Cardiac function in I/R group was lower than that in sham group, which was significantly improved by pretreatment with olprinone (P＜0.01),but systolic arterial pressure (SAP) diastolic arterial pressure (DAP) mean arterial pressure (MAP) mean pressure developed in left ventricle (Pmean) had no significant difference (P＞0.05). The percentage of myocardial infarct size in olprinone-M and olprinone-H group was lower than that in I/R group (P＜0.05).There was no significant difference in mortality among groups within 24 hours. Compared with sham group, the expressions of Caspase-3 and Bax were obviously up-regulated in I/R group (P＜0.01), whereas caspase-3 was down-regulated in olprinone-M group (P＜0.05) and Bax was inhibited by different doses of olprinone (P＜0.05), but the expression of Bcl-2 increased (P＜0.05); furthermore, the ratio of Bcl-2/Bax decreased in I/R group (P＜0.01) and increased with different degrees in different doses of olprinone (P＜0.05). Meanwhile, compared with sham group, the expression of Beclin-1 was up-regulated in I/R group(P＜0.05),and also increased in olprinone-L and olprinone-M groups(P＜0.05), but the ratio of Bcl-2 /Beclin-1 decreased in different doses of olprinone making statistically significant difference only in olprinone-M group (P＜0.05). Moreover, different doses of olprinone elevated the different ratios of LC3B/LC3A (P＜0.05), and this elevated ratio in olprinone-M group at median among groups. Conclusions Olprinone can strengthen the cardiac function after myocardial ischemia/reperfusion injury, without leading to disorders in hemodynamics; by regulating autophagy with anti-apoptotic protein, olprinone can make autophagy to an appropriate level using the mechanism of autophagy to preventing the myocardium from injury.