Effect Of Propofol On Autophagy During Myocardium Ischemia/Reperfusion In Type 2 Diabetic Rats

Objective The incidence and mortality of cardiovascular disease with type 2 diabetes mellitus(T2DM) is increasing each year. Cardiovascular disease is the most common complications in patients with T2 DM and the main cause of death. The number of T2 DM patients who die of coronary heart disease is 2-4 times that of non-T2 DM patients, a serious threat to human. Propofol, a widely used intravenous anesthetic, can protect against myocardial ischemia/reperfusion(I/R) injury by reducing oxygen free radicals and lipid peroxidation. Autophagy is a process by which impaired, denatured or aging proteins are delivered to and degraded in the lysosome. Basal autophagy is crucial for homeostasis of cells, on the contrary, excessive autophagy occurred during starvation, which can initiate a self-killing program in the form of apoptotic or autophagic cell death. In recent years, increasing studies have shown that propofol can regulate cardiomyocyte autophagy, attenuate acute myocardial I/R injury in rats. However, the influence of propofol on autophagy during myocardial I/R in type 2 diabetic rats is rarely reported. Therefore, type 2 diabetic rats are induced, using high fiet diet(HFD) feed combined with intraperitoneal injection of streptozotocin(STZ), then myocardial I/R injury models, occluding the left anterior descending coronary artery, with the time for ischemia and reperfusion being 30 min and 120 min respectively, to explore the effect and mechanism of action of propofol to autophagy during myocardial I/R in type 2 diabetic rats, as to provide theoretical basis for the clinical application of propofol.Methods A totel of 42 healthy adult male SD rats, 6~8 weeks of age, weight 200~220 g, were induced by a combination of HFD feed for 8 weeks with intraperitoneal STZ(30mg/kg) injection. Then randomly divided into 6 groups(n=7) : the sham operation group(?), which underwent sham operation without tighting of the coronary artery sutures; the myocardial I/R group(?),which were induced by occluding the left anterior descending coronary artery for 30 min, followed by 120 min of reperfusion; the myocardial I/R+low dose propofol group(?), which underwent I/R and propofol infusion at 6mg·kg-1·h-1 started 10 min before occluding the left anterior descending coronary artery;the myocardial ischemia-reperfusion+middle dose propofol group(?), which underwent I/R and propofol infusion at 12mg·kg-1·h-1 started 10 min before occluding the left anterior descending coronary artery;the myocardial I/R+low dose propofol group(?), which underwent I/R and propofol infusion at 24mg·kg-1·h-1 started 10 min before occluding the left anterior descending coronary artery; the myocardial ischemia-reperfusion+ rapamycin group( ?), which underwent I/R and intraperitoneal injected of rapamycin 2mg/kg before 30 min of I/R. Before tighting of the coronary artery and after 30 min of tighting of the coronary artery and after 120 min of reperfusion, record the HR, LVSP and ±dp/dtmax. After 120 min of reperfusion, the serum concentrations of creatine phosphate kinase(CK-MB), cardiac troponin T(c Tn T), superoxide dismutase(SOD) and malondialdehyde(MDA) was measured, the injured cardiac tissues were removed for examinating the expression of microtubule associated protein 1 light chain 3(LC3?), mammalian target of rapamycin(m TOR) and phosphorylated-mammalian target of rapamycin(p-m TOR).Results Before arterial occlusion, there were no differences among HR, LVSP, and ± dp/dtmax.After 30 min of tighting of the coronary artery, compared with group I, the HR, LVSP, and ±dp/dtmax were descreased significantly in other groups,then after 120 min of reperfusion, fuether descreased significantly(P<0.05). After 120 min of reperfusion, compared with group II, the HR, LVSP, and ±dp/dtmax were descreased significantly, the CK-MB, c Tn T and MDA were increased significantly(P<0.05), the SOD descreased significantly, the expression of m TOR increased significantly, the expression of p-m TOR descreased significantly(P<0.05) in group?; while the HR, LVSP, and ±dp/dtmax were inscreased significantly, the CK-MB,c Tn T and MDA were decreased significantly, the SOD inscreased significantly, the expression of m TOR decreased significantly, the expression of p-m TOR inscreased significantly(P<0.05) in propofol groups, among which the group ? is the most significant, then the group ? and ?.Conclusions These data suggest that propofol can effectly attenuate myocardial I/R injury by inhibiting the autophagy of cardiomyocytes by 12mg·kg-1·h-1.