促红细胞生成素对压力超负荷大鼠心肌NADPH氧化酶表达的影响

 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4 000 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。

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.