Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats

Abstract

Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.