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

作者：FU Yao; ZHOU Ji-Dong; SANG Xiao-Yu; ZHAO Qi-Tao

来源：Chinese Journal of Natural Medicines, 2021, 19(03): 161-169.

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-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 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 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.