Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan.

摘要: Activation of renal peroxisome proliferator-activated receptor α (PPARα) is renoprotective, but there no safe PPARα activator for patients with chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an angiotensin II blocker (ARB) widely prescribed CKD, activates hepatic PPARα. However, Irbe9s PPARα-activating effects and the role signalling in renoprotective Irbe are unknown. Herein, these aspects were investigated healthy kidneys wild-type (WT) Ppara -null (KO) mice murine protein-overload nephropathy (PON) model respectively. The results compared those losartan (Los), another ARB does not activate its target gene expression significantly increased only Irbe-treated WT KO or Los-treated mice, suggesting effect was Irbe-specific. Irbe-treated-PON-WT exhibited decreased urine protein excretion, tubular injury, oxidative stress (OS), pro-inflammatory apoptosis-stimulating responses, they maintenance fatty acid metabolism. Furthermore, mRNAs encoding proteins involved OS, apoptosis metabolism maintained upon treatment. These reversed by antagonist MK886 detected Irbe-treated-PON-KO mice. suggest resultant mediates effects.