Protection Of Calcium Dobesilate On Aorta Of Diabetic Rats

Background:Diabetic macro vascular disease refers to the aorta, coronary artery, basiar artery, renal artery and peripheral artery atherosclerosis. Large clinical studies have confirmed experimentally angiotensin converting into enzyme inhibitor (ACEI) can protect vascular endothelial function through various ways, thereby improving the atherosclerotic state. But because it may make hyperkalemia rise, induce acute renal failure, and cause the irritating cough as a side effect, to a certain extent restricted its clinical application. About70%～80%of diabetic patients died of diabetic macroangiopathy, hyperglycemia,high blood lipids and other factors can lead to the occurrence of atherosclerosis (AS). The basis of these alterations is related to the energy substrate coursed by insulin decrease and the alteration of enzyme system activity. Calcium dobesilate is applied to diabetic retinopathy (DR) treatment at the earlist, which is ideal drug fo the treatment of DR currently. Clinical research proved that calcium dobesilate can reduce the early diabetic nephropathy patients’microalbuminuria, but on diabetic role currently reported less. This experiment through the preparation of diabetes in the rat model,detection diabetic rats in the aorta fibrinolytic enzyme inhibition the activation thing that-1(PAI-1),matrix metalloproteinases-9(MMP-9) expression and Plasma (PAI-1) and endothelin (ET) content changes discusses benzene sulfonic acid calcium on diabetic rats large blood vessels of protection and the possible mechanism. Objective:(1)To investigate the calcium dobesilate therapeutic effect on aorta of diabetic rats; To confirm the effect of calcium dobesilate on aorta with comparision to peridopril.(2)To primitively study the possible mechanism of calcium dobesilate for aorta.Methods:50healthy mail rats,8-weeks old,8of them were randomly choosen and served as normal group, the rest were injected1%streptozotocin (STZ) intraperiton eally by70mg-kg-l,after72hours, fasting blood glucose (FBG) was measured, FBG over16.7mmol/L was considered as diabetic modal;.Then all the diabetic rats were randomly divided into five groups:diabetic group, perindopril group, low-dose group of calcium dobesilate, mid-dose group of calcium dobesilate and high-dose group of calcium dobesilate. The rats in normal group and diabetic group were given0.5%sodium carboxymethycellulose. Calcium dobesilate and perindopril were suspended in0.5%sodium carboxymethycellulose, the dose was75,150,300and0.4mg-kg-1respectively.All the animals were administrated orally.The administration lasted for8weeks, once per day.During the experiment, blood glucose and body weight were detected.After last administration, blood was drown for test, rats were sacrificed by exanguination, Aorta tissue was remained. Endothelin(ET) in plasma was measured by radioimmununoassay, the expression of plasminogen activator inhibitor-1(PAI-1) and matrix metalloproteinase-9(MMP-9) in aorta was measured by immunohistochemical stain, aorta pathological morphous was observed by light and electron microscope.Results:Compared with the diabetic group, the plasma level of ET and PAI-1were decreased(P<0.05) by calcium dobesilate. Expression of PAI-1and MMP-9in the aorta was decreased by calcium dobesilate. Rats in the DM group showed abnormal aortic ultra-structure, including incrassated intima, varicose endothelial cells, proliferation and disorder of smooth muscle cells. These phenomena were significantly alleviated in the calcium dobesilate group.Conclusion:Calcium dobesilate could protect blood vessel endothelium,postpone arteriosclerosis,stability of atheromatous plaque. The effect may be concerned with decrease of PAI-1,ET and MMP-9.