Gualou-Xiebai-Banxia decoction protects against type Ⅱ diabetes with acute myocardial ischemia by attenuating oxidative stress and apoptosis via PI3K/Akt/eNOS signaling

摘要

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 typeⅡdiabetes with acute myocardial ischemia(T2DM-AMI)rats.We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells(EPCs)apoptosis via activating PI3K(phosphatidyl inositol 3-kinase)/Akt(serine/threonine protein kinase B)/e NOS(endothelial nitric oxide synthase)signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of typeⅡdiabetes 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 m RNAs 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 m RNA 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 m RNA and protein levels of PI3 K,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.