Effects Of Oxymatrine On Controlling The Damage Of Vascular Tissue In Type 2 Diabetic Rats

Background and Objective: Type 2 Diabetes(Diabetes Mellitus, DM) has become an increasing incidence of metabolic epidemic disease, and it may trigger various kinds of cardiovascular complications which cause serious harm to human health. Dysfunction and damage of the vessel endothelial cells induced by chronic hyperglycemia and hyperlipidemia are the principal causes for the cardiovascular diseases. The early symptoms of diabetic vascular diseases include the depression of endothelial dependent vasodilatation and the activation of the inflammatory response in vessel endothelium. The aim of the project is to observe the possible role and mechanism of A2 B receptors on vascular injury of type 2 diabetic rats. Furthermore, the project will also determine whether oxymatrine can protect the vessel from diabetic damage through influencing A2 B receptors specifically, which provide new experimental evidences for the prevention and treatment of diabetes and its cardiovascular complication.Methods: Type 2 diabetic rat model was established by feeding with high glucose and high fat and injecting low-dose streptozotocin(STZ). The rats in this experiment were randomly divided into four groups: control + saline group(CONTROL), control + OMT group(CON+OMT), diabetic model + saline group(DM), diabetic model +OMT group(DM+OMT). All the drugs were administered by gavage continuously for four weeks. Experimental content: 1. Body weight, fasting blood glucose and blood pressure of the rats were measured periodically. 2. The systolic and diastolic function of thoracic aortic vascular ring of the rats in each group was determined in vitro. 3. The expression of adenosine A2 B receptor of thoracic aorta was observed using immunofluorescence in each group. 4. The expression of adenosine A2 B m RNA was detected using real-time quantitative PCR(q PCR) method. 5. The expression of adenosine A2 B protein and phosphorylation of p38 ERK1/2 JNK were detected using Western blotting. 6. The inflammatory cytokines(interleukin 1 beta, interleukin 6, tumor necrosis factor alpha) of rat’s serum were measured using enzyme-linked immunosorbent assay.Results: 1.Weight of diabetic rats is significantly lower than the normal group(p < 0.05), and the blood sugar levels are significantly higher than the normal group(p < 0.01). Oxymatrine treatment can rise weight of diabetic rats(p<0.05), but cannot significantly reduce elevated blood glucose in diabetic rats(p>0.05). Furthermore, results of systolic blood pressure(SBP) and diastolic blood pressure(DBP) showed systolic and diastolic dysfunction in type 2 diabetic rats, which can be significantly ameliorated by oxymatrine treatment(p<0.05). 2.The results of thoracic aortic vascular ring systolic and diastolic experiments in vitro showed that systolic and diastolic function of diabetic rat group significantly decreased compared with normal group, and oxymatrine treatment can significantly improve the systolic and diastolic function(p<0.05). 3. The result of immunofluorescence showed that A2 B receptor expression of thoracic aorta in the diabetic rats increased significantly, and oxymatrine treatment can reduce it. 4. The result of real-time fluorescent quantitative PCR(q PCR) showed that A2 B receptor m RNA expression of thoracic aortic blood vessel in the diabetic rats increased significantly, and oxymatrine treatment can decrease it(p < 0.01). 5. The results of Western blotting also showed that A2 B receptor protein expression of thoracic aortic blood vessel in the diabetic rats increased significantly, which can be decreased by oxymatrine treatment(p<0.01). Meanwhile phosphorylation of p38、ERK1/2 and JNK of thoracic aorta vascular proteins in diabetic rats was significantly higher than that of normal group(p<0.05), while oxymatrine treatment can reduce the degree of phosphorylation of p38、ERK1/2 and JNK in DM+OMT group compared with DM group(p<0.05). 6. The inflammatory cytokines(interleukin 1 beta, interleukin 6, tumor necrosis factor alpha) of diabetic rat’s serum were higher than normal rat, and oxymatrine treatment can decrease those cytokines of diabetic rat’s serum.Conclusion: Oxymatrine might protect vascular endothelial from damage caused by high glucose toxicity in the way of reducing the A2 B receptor expression of vascular endothelial cells in 2 diabetes mellitus rats, which might cause the decrease of inflammatory cytokines.