Abstract
Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway.
Highlights
Acute myocardial infarction (AMI) is one of the leading causes of death and disability globally (Zhou et al, 2018)
This study demonstrated that propofol preconditioning protected H9C2 cells from H2O2-induced injury and myocardium from I/R injury in Langendorff hearts in rats, which is consistent with previous studies (Lai et al, 2011; Ha et al, 2012; King et al, 2012)
Previous studies have shown that propofol exerts a cardio-protective effect on myocardial IR injury through the mitogen-activated protein kinase (MAPK)/ERK pathway, repressing the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and suppressing the TRPV4 channel with subsequent inhibition of intracellular Ca2+ overload (Halladin, 2015; Wang et al, 2019; Yan and Qi, 2019)
Summary
Acute myocardial infarction (AMI) is one of the leading causes of death and disability globally (Zhou et al, 2018). I/R injury is probably caused by the reactive oxygen species (ROS) overproduction, calcium overload, apoptosis in cardiomyocytes (Hoffman et al, 2004), and inflammatory response activation (Bartekova et al, 2018). Zhang and colleagues show that propofol reduces inflammatory cytokine and myocardial apoptosis by suppressing the Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway (Zhang et al, 2019). The change in PKC expression and activity represents an important biological process in the occurrence and development of many cardiovascular diseases such as heart failure, atherosclerosis, or hypertension (Budas et al, 2007; Steinberg, 2012). Propofol activates PKC isoforms in adult rat ventricular myocytes (Wickley et al, 2006) and protects the myocardium from I/R injury (Ko et al, 1997)
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