Renoprotective Effects And Mechanisms Of Pioglitazone Independent Of Its Hypoglycaemic Action In Diabetic Nephropathy Rats

To investigate the role and mechanism of Pioglitazone in resolution of diabetic nephropathy.Methods:The animal models were induced by STZ.Effects of pioglitazone were evaluated in these models.The ratio of KW/BW, 24 h urinary protein content and GFR were observed. The levels of MDA, T-AOC,GSH ,CuZn-SOD, CAT, GSH-Px,GR in renal tissue and the levels of T-NOS,iNOS, cNOS , NO in serum were measured.The MDA,MnSOD,NO,T-NOS, Na⁺,K⁺-ATPase , Ca²⁺-ATPase levels and RCR in the renal mitochondrial were observed.Moreover,the ultrastructure and morphology of kidney and its mitochondria were examined.Results: Increased KW/BW, 24 h urinary protein content and GFR associated with DN were significantly attenuated by pioglitazone.The increased levels of MDA and decreased levels of T-AOC.GSH ,CuZn-SOD, CAT, GSH-Px,GR in diabetic kidney tissue were significantly ameliorated by pioglitazone. Pioglitazone was significantly found to inhibit the increased levels of iNOS,NO in serum of DN.The MDA, NO/T-NOS levels was reduced and MnSOD,Na⁺,K⁺-ATPase,Ca²⁺-ATPase as well as RCR levels were elevated markedly in diabetic renel mitochondrial by pioglitazone.The abnormal morphology and ultrastructures of the renel tissue and its mitochondrial in diabetic rats were also remitted by pioglitazone.conclusion: This study suggests pioglitazone has shown beneficial effects on diabetic nephropathy. The mechanism of role of Pioglitazone may be partly correlated with its anti-oxidant action and the suppression of increased NO level as well as its protective abiliby to mitochondrial,which are independent of its effects on improving glucose metabolism.