| Background:Diabetic cardiomyopathy (DC)is a important cause of heart failure in diadetes pateints,while its mechanism is unclear. Angiotensin converting enzyme inhibitors(ACEI) is recognized to improve ventricular remodeling and the prognosis of patients with heart failure. However, its side effects such as hyperkalemia, inducing acute renal failure, and cough, may limit their clinical application.Calcium dobesilate is a micrangium protective agent, and one of the ideal drug for the treatment of diabetic retinopathy (DR). Recent studies found that it could also make good effect on diabetic nephropathy (DN). DC has similar pathophysiological basis with DR and DN. We studied calcium dobesilate effect on heart of diabetic rats.Objective:(1) To investigate the calcium dobesilate therapeutic effect on heart of diabetic rats; (2) To confirm the effect of calcium dobesilate on DC with comparison to peridopril;(3)To primitively study the passible mechanism of calcium dobesilate for DC.Methods:48 healthy male rats,8-weeks old,8 of them were randomly choosen and served as normal group, the rest were injected 1% streptozotocin(STZ) intraperitoneally by 70 mg·kg-1. After 72 hours fasting blood glucose (FBG) was measured,FBG over 16.7mmol/L was considered as diabetic model. 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 noral group and diabetic group were given 0.5% sodium carboxymethycellulose. Calcium dobesilate and perindopril were suspended in 0.5% sodium carboxymethycellulose,the dose was 75,150,300 and 0.4 mg-kg-1 respectively.All th animals were administrated orally. The administration lasted for 8weeks,once per day. During the experiment, blood glucose and body weight were detected. After last administration, blood was drown for test, rats were scarificed by exanguination, heart tissue was remained. Endothelin(ET) in plasma was measured by radioimmunoassay, the expression of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-9(MMP-9) in heart was measured by immunohistochemical stain, heart pathological morphous was observed by light and electron microscope.Results:Calcium dobesilate could decrease the CVF in diabetic heart (P<0.01) and the level of ET in plasma (P<0.05).It could also down-regulate the expression of PAI-1 and up-regulate the expression of MMP-9 in heart, ameliorate myocardial pathological lesion. There was no significant difference among the effect of mid-dose, high-dose group of calcium dobesilate and perindopril group.Conclusion:Calcium dobesilate could promote the degradation of ECM,inhibite myocardial interstitial fibrosis and ameliorate myocardial pathological lesion. The effects of mid-dose and high-dose group of calcium dobesilate were similar to ACEI. The effect may be concerned with decrease of ET,PAI-1 and increase of MMP-9.
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