ABSTRACT
OBJECTIVE@#To explore the degradation mechanism of losartan on extracellular matrix in rats with diabetic nephropathy.@*METHODS@#The rat model of diabetic nephropathy was established by streptozotozin(STZ) injection, and the rats were randomly divided into 3 groups: (a normal group, a model group and a losartan group). For 16 weeks, the serum creatinine and urea nitrogen were measured, and glomerular sclerosis index(GSI) were caculated. The expression of collagen Type IV,connective tissue growth factor and transforming growth factor-beta1 were examined by Western blot and real time-PCR respectively.@*RESULTS@#Blood urea nitrogen, GSI and the expressions of collagen Type IV and CTGF protein in the losartan group were lower than those in the model group(all P<0.05), and the expressions of collagen Type IV mRNA,TGF-beta1 mRNA and CTGF mRNA were lower than those in the model group (all P<0.05).@*CONCLUSION@#Losartan modulates glomerular sclerosis and decreases the accumulation of collagen Type IV by inhibiting TGF-beta1 and CTGF.
Subject(s)
Animals , Male , Rats , Collagen Type IV , Genetics , Connective Tissue Growth Factor , Genetics , Diabetes Mellitus, Experimental , Pathology , Diabetic Nephropathies , Metabolism , Pathology , Glomerulosclerosis, Focal Segmental , Losartan , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Random Allocation , Rats, Wistar , Transforming Growth Factor beta , GeneticsABSTRACT
OBJECTIVE@#To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction(UUO).@*METHODS@#UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly divided into a sham-operated group(n=16), a UUO model group(n=24), and an enalapril treated group(n=24). The rats were treated with 10 mg/kg.d by gastric gavage in the enalapril treated group from 24 h before the operation, and the rats were treated with the identical dose of normal saline in the other 2 groups. The rats were sacrificed at 3,7,14, and 21 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expression of collagen I (Col I) was detected by real-time PCR, and the protein expression of connective tissue growth factor (CTGF) was detected by Western blot.@*RESULTS@#The renal interstitial damage index, relative collagen area and the expression of Col I mRNA and CTGF in the renal tissues in the model group increased with the prolongation of obstruction. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, and inhibted the expression of Col I mRNA and CTGF. There was significant difference on day 3,7,and 14 (P0.05).@*CONCLUSION@#Enalapril significantly attenuates renal interstitial fibrosis by supressing the expression of Col I mRNA and CTGF.
Subject(s)
Animals , Male , Rats , Collagen Type I , Genetics , Connective Tissue Growth Factor , Genetics , Enalapril , Therapeutic Uses , Nephritis, Interstitial , Nephrosclerosis , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Ureteral ObstructionABSTRACT
OBJECTIVE@#To investigate the mechanism of losartan treating glomerulosclerosis and to observe the effect of losartan on the expressions of TGF-beta1, p-Smad2/3, and Smad7 in the renal tissues of 5/6 nephrectomized rats.@*METHODS@#Male Wistar rats were randomly divided into a sham-operated group, a 5/6 nephrectomized model group, and a losartan treated group. The rats in the model group and the losartan treated group were performed 5/6 nephrectomy by the method with 2 procedures. Twelve weeks after of the operation, all rats were killed. The 24-hour urinary protein, serum creatinine, and urea nitrogen were detected. Pathological changes of the renal tissues were observed by HE and Masson staining, and the expressions of TGF-beta1, p-Smad2/3, and Smad7 were detected by immunohistochemical staining.@*RESULTS@#The 24-hour urinary protein, serum creatinine, urea nitrogen, and the relative area of collagen in the renal tissues of the rats in the model group significantly increased (P<0.01), and losartan could reduce these indexes. The expressions of TGF-beta1 and p-Smad2/3 were just at a low level in the renal tissues of the rats in the sham-operated group, and were strongly positive in the model group; but losartan could decrease the expressions of TGF-beta1 and p-Smad2/3 (P<0.01). The expression of Smad7 in the model group was fewer than that in the sham-operated group (P<0.01), but losartan could improve the expression of Smad7 (P<0.01).@*CONCLUSION@#Losartan may implement its anti-glomerulosclerosis by affecting TGF-beta1, p-Smad2/3, and Smad7 of TGF-beta/Smads pathway of the renal tissues of 5/6 nephrectomized rats.
Subject(s)
Animals , Male , Rats , Kidney , Metabolism , Losartan , Pharmacology , Nephrectomy , Methods , Signal Transduction , Smad2 Protein , Metabolism , Smad3 Protein , Metabolism , Smad7 Protein , Metabolism , Transforming Growth Factor beta1 , MetabolismABSTRACT
OBJECTIVE@#To investigate the expression of P21 in renal interstitial fibrosis rats and the effect of enalapril on it.@*METHODS@#Sprague Dawley rats were randomly divided into 3 groups: a sham operation group,a unilateral urethral obstruction group, and an enalapril treatment group. The expression of P21 in renal tubular epithelial cells on the process was detected by immunohistochemistry at different time spots (7, 14, 21 d after UUO, sham-surgery or enalapril treatment). The expression of p21 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR).@*RESULTS@#Seven days after the surgery, significant differences were found in P21 expression between UUO and SOR renal tubular cells. With degree of interstitial fibrosis aggravating, P21 expression increased. Enalapril can inhibit its expression.@*CONCLUSION@#In the kidney of UUO rats, P21 expression increased and enalapril possessed significant inhibitory effects on the procedure. P21 may participate in the pathogenesis of renal tubule-interstitial fibrosis.
Subject(s)
Animals , Male , Rats , Angiotensin-Converting Enzyme Inhibitors , Pharmacology , Therapeutic Uses , Enalapril , Pharmacology , Therapeutic Uses , Kidney Tubules , Metabolism , Nephrosclerosis , Drug Therapy , Metabolism , Proto-Oncogene Proteins p21(ras) , Genetics , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Ureteral ObstructionABSTRACT
OBJECTIVE@#To explore the effect of p27 in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats, and to examine the expression changes of p27 after enalapril intervention and to interpret the anti-fibrotic mechanism.@*METHODS@#Ninety rats were randomly divided into the sham-operated group (SOR), UUO group,and UUO+enalapril treatment group [enalapril: 10 mg/(kg.d)]. The rats of each group were respectively sacrificed on 7, 14, 21 days post-operatively. The renal pathological changes were dynamically observed by HE. The expression and dynamic changes of p27 were detected by immunohistochemistry. The level of p27 mRNA were detected by RT-PCR.@*RESULTS@#The expression of p27 in renal tubular epithelial cells and p27 mRNA were strongly positive in the SOR group. With degree of interstitial fibrosis aggravating, the expression of p27 mRNA was gradually reducing. Enalapril could improve the expression of p27 on the 14th and 21st days after the UUO.@*CONCLUSION@#(1) This study supports a causative role of p27 in the formation of fibrosis of renal mesenchyme in rats with UUO. (2) The anti-fibrotic mechanism of enalapril is partly the improvement of p27 expression.