Abstract:

Abstract:Objective To explore the effects of atorvastatin  pretreatment (AT) on the expressions of HIF-α and VEGF protein and mRNA at different time points in myocardium tissue of the  rats after myocardium ischemia reperfusion(I/R) and to elucidate the protective effect of AT  on myocardium tissue of the rats.Methods 50 healthy male Wistar rats were randomly divided into sham operation group,ischemia 30 min reperfusion 2 h model (I30minR2h) group,ischemia 30 min reperfusion 6 h model  (I30minR6h) group,ischemia 30 min reperfusion 2 h atorvastatin (I30minR2hAT,10 mg/kg) group, and ischemia 30 min reperfusion 6 h atorvastatin (I30minR6hAT,10 mg/kg) group;there were 10 rats in each group. I/R model was prepared by ligating the left anterior descending coronary artery(LAD) method.The ratios of mypcordial infarction area of the  rats in various groups were detected,the expressions of HIF-α and VEGF protein were detected with immunohistochemical method in myocardium tissue of the  rats,the expression levels of HIF-α and VEGF mRNA in myocardium tissue of the  rats were detected by  RT-PCR method. Results Compared with sham operation group,the ratios of myocardial infarction area of the rats in I30minR2h group and I30minR6h group were increased(P<0.01);the ratios of myocardial infarction area of the rats in I30minR2h AT group and I30min R6h group were lower than those in I30minR2h group and I30minR6h group(P<0.01).Compared with sham operation group,the expression levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA in I30minR2h group,I30minR6h group,I30min R2h AT group,and  I30min R6h AT group were significantly increased (P<0.01);the expression levels of  HIF-α and VEGF protein  and HIF-α and VEGF mRNA  of the  rats in I30minR6h group  were lower than  those in  I30minR2h group,and the expression levels of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats in I30minR6h AT group  were lower than  those in  I30minR2h AT group(P<0.01).Compared with I30minR2h group,the expression levels  of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats  in I30minR2h AT group were significantly increased(P<0.01);compared with I30minR6h group,the expression levels of HIF-α and VEGF protein  and HIF-α and VEGF mRNA of the rats in I30minR6h AT group were significantly  increased (P<0.01). Conclusion I/R injury  can  early cause up-regulation of the levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA in rats,and AT  can significantly up-regulate the expression levels of HIF-α and VEGF protein and HIF-α and VEGF mRNA,which suggests that AT  has the protective effect on the myocardium tissue of rats.

Key words: myocardial ischemia reperfusion, atorvastatin, atorvastatin pretreatment, hypoxia inducible factor, vascular endothelial growth factor