2004•Zhongguo xiandai yixue/Zhongguo xiandai yixue zazhiRequires access
Influence of blocking renin-angiotensin system on renal TGFβ_1 and its significance in rat glomerulosclerosis model
Ming-hui Lin
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Abstract
Objective:To study the influence of blocking renin-angiotensin system(RAS)on gene and protein expression of transforming growth factorβ1(TGFβ1)and its significance in renal tissue of rat glomeru-losclerosis model.Methods:There were40SD rats in the study.Among them30rats were made into glomerulosclerosis models by resecting one side of kidney and injecting Adriblastine.These rats were divided randomly into glomerulosclerosis(nephrosis)group(group D),glomerulosclerosis treated with Benazepril group(group DB),glomerulosclerosis treated with Losartan group(group DL)with10rats in each group.The re-maining10ones were taken as sham-operation(control)group(group C),injected with normal saline intocaudal vein.Rats in group DB were given Benazepril(10mg/kg.d))through gastric administration.Rats in group DL were given Losartan(40mg/kg.d)through gastric administration.Rats in group C and D were given normal saline of corresponding volume every day through gastric administration.After6weeks of treatment,the expressions of TGFβ1mRNA and typeⅣcollagen(ColⅣ)mRNA in renal cortex were tested using re-verse transcription polymerase chain reaction.The expression of TGFβ1protein was tested using Western blot.The content of ColⅣin renal cortex was measured using immunohistochemical method.The renal pathologi-cal changes were analyzed.Blood albumin,cholesterol,BUN,creatinine and24-hour urine protein were test-ed.Results:Group D presented with massive proteinuria,hypoalbuminemia and hypercholesterolemia,which had a significant difference with group C(P 0.05).BUN and creatinine were elevated.There were glomerular mesangial proliferation and extracellular matrix deposit.The expressions of TGFβ1mRNA and protein in-creased3.59and2.60times respectively more than the control.The expressions of ColⅣmRNA and protein increased2.57and1.40times respectively more than the control.After6weeks of treatment with Benazepril and Losartan,blood and urine biochemical changes were significantly improved in groups DB and DL and so were the pathological changes.The expressions of TGFβ1mRNA and protein were downregulated46%,53%,55%and59%,respectively.The expression of ColⅣalso decreased.The expression of TGFβ1had signifi-cant positive correlations with glomerular extracellular matrix typeⅣcollagen,glomerular assault index(GAI)and renal tubule interstitial assault index(IAI)(P 0.05).Conclusion:Blocking RAS with Benazepril and Losartan could decrease the glomerular extracellular matrix deposit probably through the downregulation of TGFβ1mRNA and protein.