Résumé
Objective To investigate the effect of fosinopril on the expression of transforming growth factor (TGF)-activated kinase 1 (TAK-1) in the kidney of rats with unilateral ureteral obstruction (UUO),and its protective effect on renal interstitial fibrosis (RIF).Methods UUO model was induced by ligating the left ureter in rats.A total of 72 male Sprague-Wistar rats were randomly divided into 3 groups:sham-operated group (n=24),UUO model group (n=24) and UUO+fosinopril group (n=24).The rats were treated with 10 mg/(kg?d) by gastric gavage in the fosinopril treated group from 2 d after the operation,and the rats were treated with the identical dose of normal saline in the other 2 groups.Eight rats of each group were sacrificed at 7,14 and 21 d after UUO.Pathological changes of the renal tissue were observed by HE and Masson staining,and the mRNA and protein expression of TAK1 was detected by in situ hybridization,real-time PCR and Western blot analysis.Results The renal interstitial damage index of UUO group was increased compared with that of the sham-operation group (P
Résumé
Objective To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and the possible mechanisms involved.Methods The myocardial infarction rat model was reproduced.Twenty-four hours after infarction,the survived rats were randomly divided into myocardial infarction group(MI group,n=9),simvastatin 10mg group [10mg/(kg?d),Sim1 group;n=8],simvastatin 20mg group [20mg/(kg?d),Sim2 group;n=10] and simvastatin 40mg group [40mg/(kg?d),Sim4 group;n=9].A sham-operated group(Sham group;n=10) served as control.Four weeks later,the serum lipid level,hemodynamic indexes and left ventricular weight index(LVWI) were measured.The changes in rats' myocardial tissue were observed with HE staining;the cross-sectional area of myocardial cells was calculated.The expressions of transforming growth factor ?1(TGF-?1) and TGF-?-activated kinase 1(TAK1) in non-infarction area were determined by Western blotting and reverse transcription polymerase chain reaction(RT-PCR).Results The hemodynamic indexes,LVWI,cross-sectional area of myocardial cells and the pathological changes were improved,and mRNA and protein expressions of TGF-?1 and TAK1 were down-regulated significantly in the 3 Sim-treated groups compared with that in MI group.The indices mentioned above were significantly different in Sim2 and Sim4 group compared with Sim4 group(P0.05).Conclusion The inhibitory effect of simvastatin on ventricular remodeling after acute myocardial infarction is independent of its lipid-regulating effect,but possibly attributed to its action in inhibiting the TGF-?1/AK1 signal transduction.Within the concentration of 20mg/(kg?d),the therapeutic efficacy of simvastatin may be more obvious with an increase in its dosage.