Effects Of Qin Hua Yu Re Fang On Diabetic Cardiomyopathy In Rats And Possible Mechanisms

Objective:To investigate the effect of Qing hua yu re fang on rat with type 2 diabetic cardiomyopathy and to explore its mechanisms.Methods:Rats were feeded with high-sugar and high-fat diet after administration of low-dose streptozotocin in order to make diabetic cardiomyopathy model of type 2 diabetes in rats and the characteristics of animal models were observed such as:(1) Body weight, the ratio of heart weight to body weight. (2) Blood biochemical indexes:fasting blood glucose and lipid profile including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL). (3) Myocardial histopathology and ultrastructure.All animal models were divided into model group (no drug intervention), Qing hua yu re fang of high dose, middle dose and low dose group and the metformin intervention group.The roles and mechanism of Qing hua yu re fang on the pathphysiology and histochemisty of diabetic cardiomyopathy were investigated:(1) insulin resistance index, glucose infusion rate (GIR); (2) Inflammatory cytokines such as high-sensitivity c-reactive protein, serum tumour necrosi factor alpha (TNF-α) and serum adiponcetin; (3) oxidative stress indexes including superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and malondialdehyde (MDA); (4)t-PA/Plasminogen activator inhibitor-1 (t-PA/PAI-1); (5) the myocardial apoptosis of model animals; (6) gene expression of myocardial glucose transport protein4 (GluT-4).Results:(1) The body weight,the ratio of heart weight to body weight,fasting blood glucose and total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) were significantly increased compared with control group (p<0.05). The myocardial histopathological examination of the diabetic group showed that myocardial cells in diabetic rats rowed in disorder with myocardial hypertrophy, distortion, cell gap interstitial increased, perivascular accumulation of extracellular matrix components and collagen interstitial fibrosis. But myocardial cells in control group rowed densily in order with structural clarity, fewer stromal cells and only a few fibroblasts. The observation of myocardial ultrastructure by electron microscopy found myocardial mitochondrial swellen, vacuolization, fingerprint-shaped mitochondria, myofilament dissolution, fracture, intermittent intercalated disk increased, nuclear swellen, and chromatin margination in diabetic rat. Cardiomyocytes of the control group are neat, dense, cell connections clear, oval nucleus, and the structure of a large number of control mitochondria and glycogen can be seen within the cytoplasm. Qing Hua Yu Re Fang decreased the level of body weight, the ratio of heart weight to body weight,fasting serum glucose and total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL). It also improved model myocardial histopathology and ultrastructure.(2) The fasting insulin levels, insulin tesistance index (HOMA-IR),the level of inflammation cytokines (serum high-sensitivity c-reactive protein, TNF-α) and oxidative stress indexes (MDA) and plasm PAI-1 of diabetic model group were significantly increased compared with control group (p<0.05). Glucose infusion rate (GIR) and the level of serum adiponcetin, serum SOD and GSH-Px were significantly decreased compared with control group (p< 0.05) Expression of glucose transporter 4 (GluT4)mRNA in myocardial cell of rats with type 2 diabetes was also significantly decreased compared with control group (p<0.05). The number of apoptosis positive myocardial cells was significantly higher in the diabetic group than in the control group.Qing Hua Yu Re Fang increased glucose transporter 4 (GluT4) mRNA expression in myocardial cell of rats with type 2 diabetes and decreased myocardial cell apoptosis, decreased the level of inflammation cytokines such as high-sensitivity c-reactive protein and TNF-a and increased the level of serum adiponectin. Qing Hua Yu Re Fang can decreased the level of fasting serum MDA and increased the activity of SOD and GSH-PX. It also decreased the level of serum plasminogen activator inhibitor-one and decreased insulin resistance index and increased glucose infusion rate (GIR).Conclusion:(1)Qing Hua Yu Re Fang can decreased the level of body weight, the ratio of heart weight to body weight,fasting serum glucose and total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL). It also improved model myocardial histopathology and ultrastructure.(2) The mechanism of myocardial protection may be related to some factors such as it can increase glucose transporter 4 (GluT4) mRNA expression of myocardial cells,decrease the level of inflammation cytokines such as high-sensitivity c-reactive protein and TNF-a and increase the level of serum adiponectin, decreased the level of fasting serum MDA and increase the activity of SOD and GSH-PX, decrease the level of serum plasminogen activator inhibitor-one (PAI-1) and insulin resistance index and increase glucose infusion rate (GIR), improve blood stasis and decrease myocardial cell apoptosis.