Atorvastatin Exerts Protective Effect on Cardiopulmonary Bypass Induced Renal Injury in Rats via PPAR-γ

Abstract

Background: To investigate the protective effect and possible mechanism of atorvastatin pretreatment on renal function after cardiopulmonary bypass (CPB) in rats. Methods: Twenty-four adult male Sprague-Dawley (SD) rats randomly were divided into three groups: Sham operation group, CPB group, and administration group (N = 8 in each group). The caudal artery and right jugular vein were used to establish the CPB circuit for the CPB and administration groups. Drugs were administered by oral gavage one week before the operation. All rats were executed for succeeding experiments 72h after the operation. Plasma levels of creatinine (Cre) and IL-8 at different time points and levels of TNF-α and MPO in renal tissue were detected by ELISA. Renal pathological changes were observed by HE staining. PPAR-γ expression was determined by immunohistochemistry and western blot. Results: All rats survived the whole process without incident. Renal function of rats undergoing CPB was impaired to varying degrees based on the plasma Cre concentration, and atorvastatin pretreatment alleviated this effect. The concentrations of six inflammatory cytokines (IL-1β, IL-6,IL-8, IFN-γ,TNF-α, and MPO) were significantly elevated after CPB procedure, while atorvastatin pretreatment ameliorated the inflammatory condition caused by CPB. Further analysis showed that in both HK-2 cells and renal tissues, atorvastatin promoted the expression of PPAR-γ. Conclusion: Atorvastatin pretreatment exerted protective effect on CPB-associated kidney injury and inflammation in rats. The activation of PPAR-γ may contribute to the protective effect of Atorvastatin.