Propofol protects hearts from ischemia-reperfusion injury through interfering with mitochondria-dependent apoptotic pathway / 中国药理学与毒理学杂志

ABSTRACT

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 isolated Langendorff-perfused rat hearts were rendered globally ischemia for 25-min followed by 30-min reperfusion to establish I-R injury model. The cardiac function parameters were recorded. The swelling, integrity of electron transport chain (ETC) and content of malondialdehyde (MDA) in myocardium mitochondria were determined. The percentage of apoptotic cardiomyocytes and the expressions of Bcl-2 and Bax proteins were evaluated by flow cytometry. The expressions of caspases-8, -9 and -3 proteins in myocytes were detected by immunohistochemistry. RESULTS Compared with I-R group, perfusing with 30 and 60 μmol·L-1 propofol from 10 min before ischemia to whole reperfusion period resulted in improvement in cardiac function. The swelling and ETC lesion of mitochondria alleviated, and MDA content decreased. The percentage of apoptotic cardiomyocytes was markedly lower than that of I-R group. The expression of Bcl-2 protein was higher and the expression of Bax was lower than that of I-R group. The expressions of caspase-3 and caspase-9 proteins were obviously lower than those in I-R group. CONCLUSION Propofol confers significant protection against the I-R injury in the isolated rat hearts. Diminishing oxidative stress, protecting mitochondria from peroxidative injury, thus interfering with the mitochondria-dependent apoptotic pathway may be one of the major mechanisms of its cardioprotection.