The Protective Effect Of PPAR-α Agonist On PAN-induced Podocyte Injury

Objective:To investigate the function of fenofibrate on PAN-induced podocyte injury. Method:18weeks old SD female rats were randomly assigned into3group(n=6). mice in PAN group and fenofibrate treated group received a single intravenous injection of PAN (65mg/kg), while those in control group received equal volume of saline. Mice in fenofibrate treated group received40mg/(kg-d) of fenofibrate (intragastric administration) at day1after PAN injection, while those in PAN group and control group received equal volume of vehicle.24hours urine sample from all group were collected in day0(lday before PAN injection), day6, day10. The24hours urine protein was detected by Bradford Assay. All the rats were sacrificed10days after the induction of podocyte injury, glomerulus sample were collected. The expression of Podocyte injury marker and transcription level in apoptosis, podocyte cytoskeleton protein, slit diaphragm protein were evaluated by western blotting and real-time PCR. Result:Compared with the control group,10days after injection of PAN,24hours urine protein was obviously increased, the expression and transcription level of podocyte injury marker desmin, apoptosis, gap junction Cx-43, podocyte cytoskeleton protein, slit diaphragm protein were upregulated greatly, but those were significantly lower in fenofibrate treated group as compared with those in PAN group. Conclusion:PPAR-a agonist fenofibrate can ameliorate PAN-induced glomerulus podocyte injury, the mechanism involved may be associated with inhibition of the mitochondria apoptosis and TGF-β/Smad pathway.