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Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in type Ⅱ diabetes with acute myocardial ischemia (T2DM-AMI) rats.We hypothesized that GXB may display its protective effect on T2DM-AM1 by reducing endothelial progenitor cells (EPCs) apoptosis via activating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type Ⅱ diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI).Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination.The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry.Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis.The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose,muscular enzymes,and blood lipids,and reduced oxidative stress.Furthermore,EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K,Akt,and eNOS compared to the controls.Conversely,T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis,combined with increased mRNA and protein levels of PI3K,Akt,and eNOS compared to those of untreated T2DM-AMI rats.Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.