摘要
目的探讨在不同发育阶段心脏中,PPARγ抗氧化应激诱导的损伤的作用及其机制。方法通过H2O2诱发氧化应激损伤,测定不同发育阶段心肌细胞收缩率的变化;并通过RT-PCR方法测定细胞内PPARγ、超氧化物歧化酶(superoxide dismutase,mitochondrial,SOD2)和过氧化氢酶(catalase,CAT)等基因的表达水平。结果 H2O2处理前后新生白兔心肌细胞缩短率显著降低(2.44±0.27%vs1.77±0.39%,p=0.023),成年白兔组无显著改变(3.69±0.21%vs3.53±0.30%,p=0.57)。新生白兔和成年白兔心肌细胞中PPARγ和SOD2表达存在差异(0.98±0.13vs1.51±0.18,1.02±0.19vs2.36±0.24,p分别为0.007和<0.001);罗格列酮处理后新生和成年白兔心肌细胞中SOD2(1.00±0.20vs2.22±0.08,p=0.011;1.00±0.19vs1.67±0.09,p=0.025)和CAT(1.00±0.22vs2.33±0.17,p=0.008;1.00±0.15vs1.81±0.11,p=0.019)表达增加。新生白兔心肌细胞中,对照组和H2O2组之间,以及H2O2组和H2O2+ROSI组间线粒体膜完整性有显著性差异(p分别为<0.001和0.020)。在成年白兔心肌细胞中,对照组和H2O2组之间,以及H2O2组和H2O2+ROSI组间线粒体膜完整性也有显著性差异(p分别为<0.001和0.027)。结论新生白兔心肌细胞受到氧化应激所诱导的损伤更严重;在心脏发育的不同阶段,PPARγ表达量随年龄增加而逐渐增加,且其降低氧化应激所诱导的细胞损伤的机制与上调抗氧化酶SOD2和CAT基因的表达水平相关。
Objective The present study aimed to investigate the cardioprotective effect and its mechanisms of PPARγ in developing animal hearts.Methods Through the Oxidative Stress induced by H2O2,the Sarcomere shortening from isolated myocytes was measured.And the expressions of SOD2,CAT and PPARγ were detected by RT-PCR.Results 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).mRNA expression of PPARγ and 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.mRNA expression of SOD2 before and after ROSI use in newborn and adult rabbit hearts were 1.00±0.20 vs 2.22±0.08(p=0.011)and 1.00±0.19 vs 1.67±0.09(p=0.025).mRNA expression of CAT in newborn and adult animal were 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).In newborn hearts,the percentage of damaged mitochondrial between either Contro vs.H2O2 or H2O2 vs.H2O2+ROSI groups were significant respectively,(p<0.001 =0.020).This damaged percentage in adult hearts were also significant between either Contro vs.H2O2 or H2O2 vs.H2O2+ROSI gorups(p<0.001 and =0.027,respectively).Conclusions The ventricular cells of newborn rabbit are more susceptible to oxidative stress;there is significant difference in the expression of PPARγ at different stages in the developing heart;PPARγ has potential of cardioproctection to injury induced by oxidative stress in developing heart,via the up-regulation of the expressions of SOD2 and CAT genes.
出处
《中国分子心脏病学杂志》
CAS
2010年第6期366-369,共4页
Molecular Cardiology of China
