| Background:Diabetic Nephropathy(DN) is the main micrangium complications of diabetic mellitus(DM),and is the leading reason for diabetic mortality.Onste of DN is insidious and there are a lot of difficulties in treatment.In early-stage of DN,renal lesions is reversible and it is very important to give positive interference.At present, the drugs which are used for DN such as angiotensin-converting enzyme inhibitor(ACEI)and angiotensinⅡreceptor blocking pharmacon(ARB) could decrease urinary albumin significantly,and depress blood preasure,so they are clinical lot medcine for DN,but,the application is confined because of their side effect or cost. Calcium dobesilat is micrangium protective agent,and is proved had a good effect on early DN by clinical practice.We studied calcium dobesilate effect on early DN rats, investigated its pharmacodynamic action and possible pharmacology mechanism, comparied with classical ACEI to ensure the result to be persuasive,aiming at providing references for clinical application.Objective:(1) To investigate the calcium dobesilat therapeutic effect on DN rats,and compare with Perindopril,to look for new way for DN.(2) To primitively study the possible mechanism of action of calcium dobesilate for DN.Methods:50heathy mail rats,8-weeks old,8 of them were randomly choosen and served as normal group,the rest were injected 1%streptozotocin(STZ) intraperitoneally by 70mg·kg-1,after 72 hours,fasting blood glucose(FBG) was measured,FBG over 16.7mmol/L was considered as diabetic modal;when 25%of diabetic animals shown urinary albumin,DN model was regarded as successful.Then all the DN rats were randomly divided into DN blank group,0.4mg·kg-1Perndopril group,75mg·kg-1 calcium dobesilate group,150mg·kg-1 calcium dobesilate group and 300mg·kg-1 calcium dobesilate group,the rats who din't receive STZ treatment were servered as normal group.All the animals were administrated orally,rats in DN blank group and normal 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 0.4mg·kg-1 respectively.The administration lasted 8 weeks,once per day.During the experiment,blood glucose and 24-hour urinary albumin were detected,after last administration,blood was drown for test,rats were scarificed by exanguination,renal tissue was remained.Endothelin(ET) in plasma and renal cortex were measured by radioimmunoassay,the expression of plasminogen activator inhibitor-1(PAI-1) and matrix metalloproteinase-9(MMP-9) in kidney were measured by immunohistochemical stain,renal pathological morphous was observed by light and electron micoscope.Results:Calcium dobesilate could decrease 24h urinary albumin of early DN rats, and appeared dose-dependent relationship.It also decreased levels of ET both in plasma and renal cortext,down-regulated the expession of PAI-1 in kidney, up-regulated the expression of MMP-9,ameliorated renal pathological lesion,and appeared some dose-effect relationship.The effect of 300mg·kg-1 calcium dobesilate was better than 0.4mg·kg-1 Perindopril throughtout the experiment.Conclusion:Calcium dobesilate could protect blood vessel endothelium,promoted the degradatin of extracellar matrix(ECM),inhibited sclerosis and fibrosis, ameliorated the lesion of glomerular filtration structure,reduced urinary albumin, appeared dose-dependent relationship,and the effects were similar to classical ACEI. The effect may be concerned with decrease of PAI-1,ET and increase of MMP-9.
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