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Prevention Of Aristolochic Acid Nephr Opathy In Rats With Tranilast

Posted on:2008-09-14Degree:MasterType:Thesis
Country:ChinaCandidate:D D LiFull Text:PDF
GTID:2144360218960259Subject:Science within the kidney
Abstract/Summary:PDF Full Text Request
Objective: 1.To observe the change of renal function and pathology inaristolochic acid nephropathy rats which were gastric gavaged with tranilast. 2. To investigate preliminarily the changes of expression of renal TGF-pl,FN,HGF, in situ hybridization BMP-7 and Smad6 in a rat model of aristolochic acid nephropathy when they are treated by tranilast and irbesartan in order to try to elucidate the detailed mechanism of them preventing aristolochic acid nephropathy.Methods: 68 SD male rats were randomly divided into six groups of twelverats(control group have eight rats ) as follows. Control group: rats were gastric gavaged of water daily(10ml/kg.d).The rats in model and treatment groups received 20mg/kg.d AA contained in the water extract of Aristolochica manshuriensis Kom by gastric tube for 5 days in the 1st week,and later 15mg/kg.d for 7 days in everry other week up to 11th week.Besides,the rats in three tranilast therapy groups: low dose group rats were gastric gavaged of tranilast 100 mg/kg.d, moderate dose group rats were gastric gavaged of tranilast 200 mg/kg.d,high dose group rats were gastric gavaged of tranilast 400 mg/kg.d.Irbesartan therapy group: rats were gastric gavaged of irbesartan 10 mg/kg.d. The correlated targets were observed at the end of 8 weeks and 412weeks after gavage of tranilast and irbesartan . The proteins of TGF-β1,FN, HGF in every kindney were measured by immunohistochemistry(IH),the proteins of BMP-7 and Smad6 were measured by in situ hybridization .The result were investigated semiquantitatively by image analysis.Results: 1. The hemoglobin in every therapy group and model group weresignificantly higher than control group (P<0.05 ) . The creatine and protein excretion in every therapy group and model group were significantly lower than control group (P<0.05 ). 2.On histopathology tranilast attenuated tubular cells vacuolations as well as interstitial fibrosis. 3. Meanwhile, tranilast down-regulated the protein of TGF-β1,FN and up-regulated the protein of HGF,BMP-7 and Smad6 in kidney.Conclusion: Tranilast can attenuate the structural and functional changes ofkidney in aristolochic acid nephropathy rats. Decreased AA-related TGF-β1 ,FN up-regulation expression and increased AA-related HGF,BMP-7 and Smad6 down-regulation expression in the kidney may be related to mechanisms of protective effect of tranilast in the treatment of aristolochic acid nephropathy.
Keywords/Search Tags:tranilast, aristolochic acid nephropathy, nephrotoxicity
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