目的：探讨促红细胞生成素（ EPO）对压力超负荷大鼠心肌NADPH氧化酶的影响。方法：36只SD雄性大鼠，腹主动脉结扎复制压力超负荷心肌肥大模型。动物随机分成3组：模型组；假手术组：除不缩窄腹主动脉外，其余操作同腹主动脉缩窄组；重组人促红细胞生成素（ rhEPO）治疗组（ EPO治疗组）：术后给予rhEPO，腹腔注射4000 U/kg，每周2次。8周后采用心动超声和血流动力学评价心功能；Masson染色观察心肌纤维化程度；实时定量PCR法和Western blotting法检测NADPH氧化酶2（ Nox2）和Nox4 mRNA及蛋白表达的变化；Western blotting法观察心肌炎症因子CD45、F4/80和转化生长因子β（ TGF-β）的表达变化。结果：与模型组比较，EPO治疗组左室射血分数（LVEF）、左室短轴缩短率（LVFS）、左室收缩末压（LVESP）及左室内压最大上升和下降速率（±dp/dtmax）明显升高（ P＜0.01），左室收缩末内径（LVESD）、舒张末内径（LVEDD）及左室舒张末压（LVEDP）下降（P＜0.01）；同时，EPO可降低压力超负荷所致的心肌纤维化程度（P＜0.01），降低心室肌中 Nox2、Nox4 mRNA和蛋白的表达（P＜0．05或P＜0．01）及心肌炎症因子CD45、F4/80、TGF-β蛋白的表达。结论： EPO可抑制压力超负荷所致大鼠的心肌纤维化，改善心功能，其机制可能与降低NADPH氧化酶活性，抑制心肌氧化应激水平，减少心肌炎症反应有关。%AIM:To explore the effect of erythropoietin ( EPO) on the expression of myocardial NADPH oxi-dase (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 func-tions.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 inflam-matory factors CD45, F4/80 and TGF-βwere 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 ex-pression of Nox2 and Nox4 at mRNA and protein levels in the myocardium (P<0.05 or P<0.01), and reduced the pro-tein 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.
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