科研之友
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摘要
Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPAR alpha agonist fenofibrate and PPAR gamma agonist pioglitazone were also assessed in a 1% ethylene glycolinduced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPAR alpha and PPAR gamma expression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPAR alpha localized to the cytoplasm of both proximal and distal tubular cells, whereas PPAR gamma accumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibratetreated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPAR gamma suppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPAR alpha may elicit the opposite effect.
- 出版日期2016
- 单位沈阳医学院
