YM-0074) was purchased from Shanghai Yuanmu Biotech Co., Ltd. Also, the H9c2 cardiomyocytes were treated with different concentrations of OMT (0, 10, 30, 50, 70 and 90 µM) for 12 h under normoxic conditions to assess their cytotoxicity and select the concentrations for further analysis. Therefore, a hypoxia/reoxygenation (H/R) model of H9c2 cardiomyocytes was established in the present study to detect the potential effects and signaling pathways of OMT.Ĭell groups were established and the concentrations and durations of treatment chosen with reference to previously published methods ( 14, 16, 17). However, the effects of OMT on I/R injury in cardiomyocytes, and the specific signaling pathways by which OMT exerts these effects have not yet been explored. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) pathway are important pathophysiological mechanisms that are relevant to I/R injury, and previous studies have shown that OMT attenuates I/R injury in the brain through the p-Akt/GSK3β/HO-1/Nrf2 signaling pathway ( 12-14). The use of OMT in patients with cardiovascular diseases has attracted increasing attention, because studies have identified that OMT has a wide range of pharmacological properties, including activities against arrhythmia ( 9), shock ( 10) and hypertension ( 11). Oxymatrine (OMT), an alkaloid that originates from the traditional Chinese herb Sophora flavescens Aiton, possesses numerous pharmacological properties, including anti-hepatic fibrosis ( 6), anti-inflammatory ( 7) and antitumor activities ( 8). Therefore, the search for a drug that is able to prevent or treat myocardial I/R injury is a popular focus of research. According to previous studies, I/R injury is associated with calcium overload ( 3), oxidative stress ( 4) and myocardial apoptosis ( 5). Therefore, I/R injury is an important concern of doctors following cardiac surgery. With the advent of cardiac surgery, including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG), some clinical symptoms have been alleviated, but ischemia/reperfusion (I/R) injury induces arrhythmia, heart failure and cardiomyocyte death ( 2). Coronary heart disease (CHD) is a leading cause of death all over the world according to the World Health Organization ( 1). Ischemic heart disease (IHD) has become a major public human issue, with a decreasing age of onset. These findings indicate that OMT could be a potential therapeutic candidate for the treatment of myocardial ischemia/reperfusion injury. In addition, the protective effect of OMT was shown to be associated with the PI3K/Akt signaling pathway, and the PI3K inhibitor LY294002 attenuated the effects of OMT on the H9c2 cardiomyocytes exposed to H/R. Furthermore, the OMT pretreatment reduced the expression of Bax and caspase-3, while inducing Bcl-2 expression. The OMT pretreatment decreased the production of MDA by reactive oxygen species and increased the activities of SOD and CAT. The results revealed that OMT increased the viability of H9c2 cardiomyocytes exposed to H/R. Apoptosis was detected using TUNEL staining and flow cytometric analysis, and the underlying mechanism was investigated using reverse transcription-quantitative PCR and western blot analyses. Oxidative stress was detected by measuring cellular malondialdehyde (MDA) content, as well as superoxide dismutase (SOD) and catalase (CAT) activities. Cell viability was measured using the MTT assay, lactate dehydrogenase release measurements and hematoxylin and eosin staining. A hypoxia/reoxygenation (H/R) model was established using H9c2 cardiomyocytes to investigate the possible positive effect of oxymatrine (OMT), an alkaloid originating from the traditional Chinese herb Sophora flavescens Aiton, on cardiomyocytes exposed to H/R injury and the underlying molecular mechanisms. Ischemia-reperfusion (I/R) plays an important role in myocardial damage, which has been widely recognized as a key procedure in the cardiovascular disease.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |