Effect of erythropoietin on expression of myocardial NADPH oxidase in pressure overload rats

AIM:To explore the effect of erythropoietin （EPO） on the expression of myocardial NADPH oxidase （Nox） in the pressure overload rats. METHODS:Male SD rats (n=36) were used to establish a pressure overload myocardial hypertrophy model by abdominal aorta ligation. The animals were divided into model group, control group (sham, without narrowing abdominal aorta, the rest of the operation was the same as the model) and recombinant human erythropoietin (rhEPO) treatment group (intraperitoneal injection of rhEPO postoperatively, 4 000 U/kg, twice a week). After 8 weeks, the cardiac ultrasound imaging and hemodynamic evaluation were conducted to determine the cardiac functions. Masson staining was used to observe the degree of myocardial fibrosis. The expression of Nox2 and Nox4 at mRNA and protein levels was detected by real-time quantitative PCR and Western blotting. The protein levels of myocardial inflammatory factors CD45, F4/80 and TGF-β were determined by Western blotting. RESULTS:Compared with model group, the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic pressure (LVESP) and left ventricular pressure maximum rising and falling rates (±dp/dtmax) increased significantly in EPO treatment group (P<0.01). At the same time, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-diastolic pressure (LVEDP) were decreased in EPO treatment group (P<0.01). EPO reduced the degree of myocardial fibrosis caused by pressure overload (P<0.01) and decreased the expression of Nox2 and Nox4 at mRNA and protein levels in the myocardium (P<0.05 or P<0.01), and reduced the protein expression of myocardial inflammatory factors CD45, F4/80 and TGF-β. CONCLUSION: EPO inhibits rat myocar-dial fibrosis induced by pressure overload, improves heart functions by decreasing NADPH oxidase activity and inhibiting myocardial oxidative stress levels and myocardial inflammatory reaction.