Effects of Danshensu on Myocardial Mitochondrial Function in Diabetes Cardiomyopathy Rats Based on PPARγ/PGC-1α Pathway
Objective To explore the effect of Danshensu on myocardial mitochondrial function in diabetes cardiomyopathy(DCM)rats based on peroxisome proliferator-activated receptor γ(PPARγ)/peroxisome proliferator-activated receptor γ co-activator-1α(PGC-1α)pathway.Methods Rats were randomly separated into normal group,model group,low-(5 mg·kg-1),medium-(10 mg·kg-1)and high-(20 mg·kg-1)dose Danshensu groups,metformin group(140 mg·kg-1),as well as high-dose Danshensu+GW9662 group(20 mg·kg-1 Danshensu+1 mg·kg-1 GW9662),with 12 rats in each group.Except for the normal group,rats in other groups were fed with high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin to construct a DCM model.After successful modeling,the rats were administered corresponding drug once a day for six weeks.Fasting blood glucose values were detected by blood glucose meter.Echocardiography was applied to evaluate cardiac function of rats including left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF).HE staining was applied to detect pathological changes in myocardial tissue.Transmission electron microscopy was applied to observe mitochondrial structure of myocardial tissue.JC-1 staining was applied to detect mitochondrial membrane potential in rat cardiomyocytes.The kit was applied to detect adenosine triphosphate(ATP)content and reactive oxygen species(ROS)expression in myocardial tissue.Western Blot was applied to detect the protein expression of PPARγ and PGC-1α in myocardial tissue.Results Compared with normal group,fasting blood glucose in model group was significantly increased(P＜0.05),LVFS and LVEF were significantly decreased(P＜0.05).It was found that myocardial tissue was obviously damaged and myocardial mitochondria became swollen.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly decreased(P＜0.05).ATP content in myocardial tissue was significantly decreased(P＜0.05),ROS expression was significantly increased(P＜0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly downregulated(P＜0.05).Compared with model group,fasting blood glucose levels in Danshensu and metformin groups were significantly decreased(P＜0.05),while LVFS and LVEF were significantly increased(P＜0.05).It was found that myocardial tissue damage and mitochondrial structure damage were alleviated.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly increased(P＜0.05).ATP content in myocardial tissue was significantly increased(P＜0.05),ROS expression was significantly decreased(P＜0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly upregulated(P＜0.05).Compared with high-dose Danshensu group,fasting blood glucose level in high-dose Danshensu+GW9662 group was significantly increased(P＜0.05),LVFS and LVEF levels were significantly decreased(P＜0.05).Damage of myocardial tissue and myocardial mitochondria structure became serious and myocardial mitochondria was obviously swollen.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly decreased(P＜0.05).ATP content in myocardial tissue was significantly decreased(P＜0.05),ROS expression was significantly increased(P＜0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly downregulated(P＜0.05).Conclusion Danshensu improves mitochondrial function in DCM rats,which may be related to the activation of the PPARγ/PGC-1α pathway.
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