[Effects of propofol on cardiomyocytes apoptosis and its mechanism after ischemia/reperfusion injury in isolated rat hearts].

AIM: To investigate the protective effect of propofol on ischemia/reperfusion (I/R) injury in isolated rat hearts and clarify the possible molecular mechanism from oxidative stress and the apoptosis initiated by mitochondria pathway. METHODS: The Langendorff model of ischemia/reperfusion was used. Forty isolated perfused rat hearts were randomly divided into control, I/R, propofol 15, 30, 60 micromol x L(-1) groups. Hearts were suffered globally ischemia for 25 min and 30 min with reperfusion. The cardiac function indexes such as the left ventricular developed pressure (LVDP), the left ventricular end diastolic pressure (LVDEP), heart rate (HR), coronary arterial flow (CF) were recorded at the time of equilibration, before ischemia, the end of reperfusion respectively. The lactate dehydrogenase (LDH), creatine kinase (CK) activities in the flow were measured. The swelling and activity of mitochondria, the activity of manganese superoxide dismutase (Mn-SOD) and content of malondialdehyde (MDA) in myocardium mitochondria were also determined. The incidence of cardiomyocyte of apoptosis and the expression of Bcl-2 and Bax were evaluated by Flow Cytometry (FCM). The expression of caspase-3, 8, 9 was detected by immunohistochemistry. RESULTS: Compared with I/R group, administration of propofol at the concentration of 30 and 60 micromol x L(-1) markedly ameliorated the cardiac function in CF, LVDP and LVDEP (P < 0.05), distinctly reduced the activities of the LDH and CK in the flow (P < 0.05) and the mitochondrial swelling, the content of MDA in myocardium mitochondria (P < 0.05), and significantly enhanced the activity of Mn-SOD in myocardium mitochondria (P < 0.05). The apoptotic index in propofol 30, 60 micromol x L(-1) group was markedly lower than that of I/R group. The expression of Bcl-2 protein in 30, 60 micromol x L(-1) propofol was higher than that of I/R group (P < 0.05). The expressions of Bax, caspase-9, 3 protein in 30, 60 micromol x L(-1) propofol were obviously lower than those of I/R group( P < 0.05). There was no significant difference in expression of caspase-8 between propofol administrated groups and I/R group. CONCLUSION: It could be concluded that propofol administrated before ischemia and during reperfusion has cardioprotective effects on ischemia/reperfusion injury in the isolated rat heart. The effect is associated with diminishing oxidative stress, protecting mitochondria from peroxidative injury, thus interfering with the mitochondria-dependent apoptotic pathway might be one of the major mechanisms of its cardioprotection.