Experimental Study Of Protective Effects Of Tranilast On Adriamycin Nephropathy In Rats

Objective To investigate the protecting effect of tranilast on the kidney ofthe rats with uninephrectomized adriamycin-induced glomerulosclerosis andstudy its possible mechanisms.Methods 72 Male Sprague-Dawley rats were randomly assigned to 5groups: normal control group, model group, irbesartan treatment group,tranilast 200 mg/kg treatment group and tranilast 400 mg/kg treatment group.The rats of normal control group were injected with normal saline via the tailvein. The rats of the other groups were uninephrectomized and injected withadriamycin 5mg/kg via the tail vein one week later. Rats of the control groupreceived distilled water via gavage. Rats of model group received sodiumcarboxymethycellulose via gavage. Rats of irbesartan treatment groupreceived irbesartan 10mg/kg.d via gavage. Rats of tranilast 200 mg/kgand 400 mg/kg treatment group received tranilast 200mg/kg.d and 400mg/kg.d via gavage. After the treatment, rats were sacrificed at the end ofweeks 4 and 8. The body weight, 24 hours urinary protein, BUN and Scrwere measured at the end of the study. Renal pathological changes wereevaluated. Immunohistochemistry was used to examine the expression of CTGF, FN, TGF-β₁, and TIMP-1 in the kidney. In situ hybridization wasused to measure the expression ofα-SMAmRNA in the kidney.Results 1.Weight of rats of model group was significantly lower comparedwith the other groups, (P＜0.05); weight lost were markedly delayed afteradministration of tranilast and irbesartan; 2.Compared with the modelgroup, proteinuria and Scr of rats treated with tranilast were significantlyreduced (P＜0.05); 3. Compared with model group, rats of tranilasttreatment groups'renal pathological change are decreased and glomerularsclerosis is markly lower; 4. Immunohistochemstry analysis shows tranilastcan decrease the expression of CTGF, TGF-β₁, FN, TIMP-1 in the kidneyof rats with adriamycin nephropathy; 5. In situ hybridization shows tranilastcan reduce the expression ofα-SMAmRNA in the kidney in adriamycinnephropathy rats.Conelusion Tranilast can effectively decrease Scr, urine protein, andrelease glomerulus pathologic injury of adriamycin nephropathy rats.Tranilast has a renoprotective effect on adriamycin-indeced nephroticsyndrome in rats. The mechanism may be relative with that tranilast candepress the expression of TGF-β₁, CTGF and TIMP-1 in the kidney, as aresult, it can drease the synthesis and secretion of extracellular matrix suchas FN. And tranilast inhibited the transdifferentation of renal primary cells,regulate the synthesis and degradation system of extracellular matrix, so itcan inhibit the progressive trend to glomerulosclerosis.