Cardioprotective Effects And Mechanisms Of Pparγ On Injury Induced By Oxidative Stress In Developing Heart

Objective Previous studies showed that peroxisome proliferator-activated receptor gamma(PPARγ) could protect heart from oxidative stress by regulating the expression of mitochondrial superoxide dismutase(SOD2) gene and catalase (CAT) gene. However, the mechanisms remainds to be unclear. The present study aimed to investigate the cardioprotective effect and its mechanisms of PPARγin developing animal hearts, via comparing different expressions of PPARγand antioxidative gene between in newborn vs in adult rabbit hearts with oxidative stress model.Methods Hearts from Zealand white adult (3-4 months, n=20) and newborn (1-4 days, n=20) rabbits were removed via thoracotomy, and the aorta was cannulated, mounted on a Langendorff apparatus and perfused with oxygenated, Tyrode's solution with or without ROSI for 90 minutes. All animals were randomly assigned as Control (perfused by Tyrode's solution for 120 mins), H2O2 (perfused by Tyrode's solution for 90 mins, followed by 200μM H2O2 for 30 mins), ROSI (perfused by 1μM ROSI for 120 mins), H2O2+ROSI (perfused by 1μM ROSI for 90 mins, followed by 200μM H2O2 for 30 mins) groups. Single ventricular cells were obtained from adult and newborn rabbit hearts by enzymatic disassociation. The cell pellets were used for RT-PCR. The expressions of proteins of SOD2 and PPARγwere detected by Western blotting. Sarcomere shortening from isolated myocytes were calculated by using an ionoptix myocyte contractility measurement system.Results (1) In response to PPARγ, perfusion with H2O2 was associated with significant reduction in sarcomere shorting (2.44±0.27% vs. 1.77±0.39%, p=0.023) in newborn rabbits, without meaningful difference in adult rabbits (3.69±0.21% vs. 3.53±0.30%, p=0.57); (2) mRNA expression of PPARγand SOD2 in newborn and adult rabbit hearts was 0.98±0.13 vs 1.51±0.18(p=0.007) and 1.02±0.19 vs 2.36±0.24(p<0.001), respectively;(3)In ROSI subgroup, mRNA expression of SOD2 in before and after ROSI use in newborn and adult rabbit hearts were 1.00±0.20 vs 2.22±0.08(p=0.011); 1.00±0.19 vs 1.67±0.09(p=0.025), with mRNA expression of CAT in newborn and adult animal 1.00±0.22 vs 2.33±0.17(p=0.008) and 1.00±0.15 vs 1.81±0.11(p=0.019), respectively; (4) in newborn hearts, the percentage of damaged mitochondrial in Control, H2O2,, H2O2+ROSI and ROSIsubgroup was 25.3±2.3%, 52.5±3.4%,36.7±5.8% and 27.2±5.0%, respectively, with sifgnificant difference between either Contro vs. H2O2 (p<0.001), or H2O2 vs. H2O2+ROSI (p=0.020). This damaged percentage in four subgroups in adult hearts was 20.1±2.4% , 40.2±3.5% , 30.1±3.5% and 22.4±4.1% , respectively, with significant difference between either Control vs.H2O2, or H2O2 vs.H2O2+ROSI subgroups(p < 0.001 and =0.027, respectively).Conclusions (1) The ventricular cells of newborn rabbit are more susceptible to oxidative stress caused by acute application of H2O2; (2) There wsa significant difference in expression of PPARγat different stages in developing heart, (3) PPARγhas potential of cardioproctection to injury by H2O2 in developing heart, via the up-regulation of the expressions of SOD2 and CAT genes.