The Ligand Of PPARγ Protects Acute Kidney Injury In Sepsis

Objective:To investigate the effects of rosiglitazone, the ligand of peroxisome proliferators-activated receptor γ(PPARγ), on the structure and function of the kidney of rats in sepsis with acute kidney injury, and the changes in expression level of apoptosis regulation genes Bcl-2in sepsis renal tissue, to provide the theory basis for the effect of PPARγ in sepsis with acute kidney injury.Materials and methods:Ninety-six male Sprague-Dawley rats were randomly divided into4groups:cecal ligation puncture and rosiglitazone group (group CLP+ROSI), cecal ligation puncture group (group CLP), sham and rosiglitazone group (group Sham+ROSI), sham group (group Sham). Setting up the sepsis model by cecal ligation puncture (CLP), group CLP+ROSI and group CLP were intraperitoneal injected with ROSI (10mg/kg) or its vehicle (dimethyl sulphoxide, DMSO)30min before CLP. Group Sham+ROSI and group Sham were also pretreated with ROSI or DMSO. Six rats were sacrificed at0,6,12,24h after CLP respectively in each group. Serum was collceted for the measurement of the level of serum creatinine and tumor necrosis factor a (TNFa), the general status of rats was observed and H&E staining was applied to detect renal pathological histology changes. Myeloperoxidase(MPO) was measured in kidney tissues. Expression of PPARγ and Bcl-2were also determined by Western blot analysis. Statistics was analyzed by SPSS13.0software application of independent samples t test, P<0.05means that the difference is statistically significant.Results:The creatinine level of Group CLP was increased with the extension of time, there was no statistically significant difference between group CLP and group Sham at6h (P6=0.812, P>0.05). The creatinine level of group CLP was significantly higher than that of group Sham at12h and24h (P12=0.047, P24=0.001, P<0.05). The creatinine level between group CLP+ROSI and group Sham+ROSI was no statistically significant difference at6h (P6=0.868, P>0.05). The creatinine level of group CLP+ROSI was significantly higher than that of group Sham+ROSI at12h and24h (P12=0.033P24=0.039, P<0.05). The creatinine level was no statistically significant difference between group CLP+ROSI and group CLP at Oh and6h (P0=0.418, P6=0.528, P>0.05). The increased creatinine level of group CLP+ROSI was significantly lower than that of group CLP at12h and24h (P12=0.04, P24=0.006, P<0.05). The TNFa concentration of group CLP was significantly higher than that of group Sham at6h,12h and24h (P6=0.00,P12=0.00, P24=0.00, P<0.05). The TNFa concentration of group CLP+ROSI was significantly higher than that of group Sham+ROSI at6h,12h and24h (P6=0.00,P12=0.00, P24=0.00, P<0.05). The increased TNFa concentration of group CLP+ROSI was significantly lower than that of group CLP at6h,12h and24h (Pe=0.01, P12=0.02, P24=0.01, P<0.05). The MPO activity of kidney tissue was no statistically significant difference between group CLP+ROSI and group CLP at Oh and6h (Po=0.875, P6=0.13, P>0.05). The increased MPO activity of group CLP+ROSI was significantly lower than that of group CLP at12h and24h (P12=0.01, P24=0.006, P<0.05). The MPO activity of group CLP was significantly higher than that of group Sham at6h,12h and24h (P6=0.00,P12=0.00, P24=0.00, P<0.05). The MPO activity of group CLP+ROSI was significantly higher than that of group Sham+ROSI at6h,12h and24h (P6=0.00, P12=0.00, P24=0.00, P<0.05). Compared with group Sham and group Sham+ROSI, in rats of group CLP and group CLP+ROSI the symptoms of sepsis and organ dysfunction were observed. The symptoms of sepsis and organ dysfunction of group CLP+ROSI were significantly reduced than that of group CLP. Expression of PPARy and Bcl-2were determined by Western blot analysis, the expression of PPARy and Bcl-2of group CLP+ROSI was significantly lower than that of group CLP.Conclusion:Rosiglitazone, as the ligand of peroxisome proliferators-activated receptor y (PPARy), reduced the inflammatory response in sepsis, decreased the apoptosis of kidney cell, improved the renal function, reduced kidney injury, and protected acute kidney injury in rats of sepsis.