Abstract
BackgroundMyocardial infarction (MI) is an acute and fatal condition that threatens human health. Dl-3-n-butylphthalide (NBP) has been used for the treatment of acute ischemic stroke. Mitochondria may play a protective role in MI injury. However, there are few reports on the cardioprotective effect of NBP or the potential mitochondrial mechanism for the NBP-induced protection against cardiac ischemia injury. We investigated the therapeutic effects of NBP in an in vivo MI model and an in vitro oxidative stress model, as well as the potential mitochondrial mechanism.MethodsThis study comprised two different experiments. The aim of experiment 1 was to determine the protective effects of NBP on MI and the underlying mechanisms in vivo. In part 1, myocardial infarct size was measured by staining with 2,3,5-triphenyltetrazoliumchloride (TTC). Myocardial enzymes and mitochondrial enzymes were assayed. The aim of experiment 2 was to investigate the role of NBP in H2O2-induced myocardial ischemic injury in H9c2 cells and to determine the potential mechanism. In part 2, H9c2 cell viability was evaluated. ROS levels, mitochondrial morphology, and mitochondrial membrane potential of H9c2 cells were measured. ATP levels were evaluated using an assay kit; mitochondrial DNA (mtDNA), the expressions of NRF-1 and TFAM, and mitochondrial biogenesis factors were determined.ResultsNBP treatment significantly reduced the infarct ratio, as observed by TTC staining, decreased serum myocardial enzymes in MI, and restored heart mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and a-ketoglutarate dehydrogenase (a-KGDH) activities after MI. Moreover, in in vitro studies, NBP significantly increased the viability of H9c2 cells in a dose-dependent manner, reduced cell apoptosis, protected mitochondrial functions, elevated the cellular ATP levels, and promoted H2O2-induced mitochondrial biogenesis in H9c2 cardiomyoblasts.ConclusionCollectively, the results from both the in vivo and in vitro experiments suggested that NBP exerted a cardioprotective effect on cardiac ischemic injury via the regulation of mitochondrial function and biogenesis.
Highlights
Myocardial infarction (MI) is an acute and fatal condition that threatens human health
These results revealed that NBP significantly improved the functional recovery after MI
Quantitative data demonstrated that NBP attenuated the loss of membrane potential (MMP) induced by H2O2 in H9c2 cells (Fig. 5c and d). These findings provided evidence that NBP exerted a protective effect against oxidative stress on the mitochondrial function in H9c2 cells
Summary
Myocardial infarction (MI) is an acute and fatal condition that threatens human health. Mitochondria may play a protective role in MI injury. There are few reports on the cardioprotective effect of NBP or the potential mitochondrial mechanism for the NBP-induced protection against cardiac ischemia injury. We investigated the therapeutic effects of NBP in an in vivo MI model and an in vitro oxidative stress model, as well as the potential mitochondrial mechanism. It has been reported that the protection of mitochondria in the post-infarct myocardium resulted in decreased mitochondrial dysfunction and cardiomyocyte apoptosis [6]. Researchers have shown that oxidative stress plays an important role in myocardial ischemic injury [8, 9]. Ischemic oxidative stress results in the reduction of myocardial antioxidants, loss of mitochondrial membrane potential, and release of superoxide [10, 11]. The identification of a pharmacological agent that exerts protective effects in mitochondria and alleviates MI injury might be an ideal cardioprotective strategy
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