Title: Effects of Pioglitazone on Renal Fibrosis of Uninephrectomized Diabetic Rats and Involved Mechanisms
Abstract:Purpose To study the effects of pioglitazone on the renal fibrosis of uninephrectomized diabetic rats and its possible mechanisms. Methods Uninephrectomized male Wistar rats (180-200 g) were randomly ...Purpose To study the effects of pioglitazone on the renal fibrosis of uninephrectomized diabetic rats and its possible mechanisms. Methods Uninephrectomized male Wistar rats (180-200 g) were randomly assigned to four groups: non-diabetic control rats (CTR), non-diabetic rats treated with 3 mg/ (kg·d) pioglitazone (CTR+P) ,low dose (35 mg/kg) streptozotocin-induced diabetic rats (DM),and 3 mg/(kg·d) pioglitazone-treated diabetic rats(DM+ P). After 10 weeks of treatment,blood glucose,serum triglyceride ,serum total cholesterol,systolic blood pressure(SBP) ,24-hour urinary protein excretion and left kidney weight/body weight (LK/BW) were examined. Periodic acid-schiff (PAS) stain was used to measure the glomerular extracelluar matrix deposition. Northern blot was used to detect the mRNA levels of transforming growth factor (TGF)-β1 and tissue inhibitor of metalloproteinases (TIMP)-1 in renal cortex. The protein expressions of plasminogen activator inhibitor (PAI)-1 in the renal cortex were also measured by Western blot. Results Compared with the CTR and the CTR + P,DM demonstrated hyperglycemia.hy-perlipidemia, hypertension and significantly increased urinary protein excretion and LK/BW, extracellular matrix (ECM) was also increased in this group. These changes were associated with significantly upregulated TGF-β1 and TIMP-1 mRNA and PAI-1 protein expression in the renal cortex. Compared with the DM group,administration of pioglitazone significantly attenuated the proteinuria, increased LK/BW and ECM, but not hyperglycemia,hyperlipidemia and hypertension ,it also ameliorated the upregulated mRNA levels of TGF-β1 and TIMP-1 and the increased protein expression of PAI-1. Conclusions Our results suggested that pioglitazone might delay the renal fibrotic progress of the uninephrectomized diabetic rats without metabolic effects. The downregulated gene expression of TGF-J31 ,TIMP-1 and PAM by pioglitazone might be involved.Read More
Publication Year: 2003
Publication Date: 2003-01-01
Language: en
Type: article
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