Effect of propofol on myocardial ischemia-reperfusion injury through MAPK/ERK pathway

OBJECTIVE: The aim of this study was to investigate the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. MATERIALS AND METHODS: Primary cells were first isolated from rats. The effects of propofol on the apoptosis of primary myocardial cells and the expression of apoptosis-related proteins were detected via flow cytometry and Western blotting, respectively. Meanwhile, the effect of propofol on MIRI model after ischemia for 2 h and reperfusion for 24 h was detected as well. Subsequently. the effect of propofol on the activity of proteins in myocardial tissues was detected using transcriptome sequencing and VI-PER method. The effect of propofol on myocardial tissues was detected via 2, 3. 5- triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Masson staining. Besides, the effect of propofol on myocardial function was detected using the BL-420F hemodynamic system. Propofol effect on the MAPK/ERK signaling pathway was determined via Western blotting in vivo. Finally, the effects of propofol on the content of serum lactate dehydrogenase (LDH), creatine kinase (CK), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected using relevant kits. RESULTS: Propofol activated the MAPK/ERK signaling pathway in a dose-dependent manner in primary myocardial cells, which also reduced the apoptotic rate of myocardial cells. The results of TTC staining, HE staining, and Masson staining showed that propofol significantly reduced MIRI in a dose-dependent manner in vivo. ERK inhibitor PD-98059 could significantly reduce the cardioprotective effect of propofol. Propofol significantly decreased the content of serum LDH. CK, and MDA (p<0.05), while it increased the content of T-SOD (p<0.05). According to the hemodynamic study, statistically significant differences were observed in left ventricular systolic pressure (LVSP), maximal rate of the decrease of left ventricular pressure (-dp/dtmax), and left ventricular end-diastolic pressure (LVEDP) between propofol group and model group (p<0.01). The results of Western blotting revealed that propofol increased the protein expression level of p-ERK1/2 in a doseand time-dependent manner in vivo. Furthermore, the expression level of p-ERK1/2 remarkably increased at 8 h after ischemia-reperfusion. CONCLUSIONS: Propofol exerts a cardio-protective effect on MIRI through the MAPK/ERK pathway.