Luo Liyun, Chen Bairong, Huang Yin, Liang Zibin, Li Songbiao, Yin Yuelan, Chen Jian, Wu Wei
Department of Cardiology.
Department of Oncological Radiotherapy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People's Republic of China.
Drug Des Devel Ther. 2016 Oct 28;10:3483-3492. doi: 10.2147/DDDT.S117683. eCollection 2016.
Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI.
Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson's staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed.
Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group (<0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group (<0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group (<0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group (<0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group (<0.01).
Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l-arginine have a more pronounced, synergistic protective effect on myocardial protection compared with that of exogenous PlGF therapy alone.
外源性给予胎盘生长因子（PlGF）可刺激血管生成，并改善急性心肌梗死（AMI）后的心室重构，补充L-精氨酸可改善内皮功能。本研究的目的是在大鼠AMI模型中比较PlGF与L-精氨酸联合治疗与单独直接给予PlGF的心脏保护作用。
50只雄性Sprague Dawley大鼠随机分为五组：假手术组、生理盐水组、L-精氨酸组、PlGF组和联合组（PlGF + L-精氨酸）。通过结扎冠状动脉左前降支建立AMI大鼠模型。结扎后治疗4周后，研究心脏功能、瘢痕面积、血管生成和动脉生成、心肌内皮型一氧化氮合酶（eNOS）和I型胶原蛋白含量以及血浆脑钠肽（BNP）浓度。进行了超声心动图、Masson染色、免疫组织化学分析、蛋白质印迹法和酶联免疫吸附测定。
PlGF组的左心室射血分数（LVEF）、左心室缩短分数（LVFS）以及毛细血管和小动脉密度均高于生理盐水组（<0.01）。PlGF组的瘢痕面积、I型胶原蛋白含量和血浆BNP浓度降低（<0.01）。L-精氨酸组和PlGF + L-精氨酸组的心肌eNOS蛋白水平升高（<0.01）。与PlGF组相比，联合组的LVEF、LVFS、心肌eNOS以及毛细血管和小动脉密度更高（<0.01）。联合组的瘢痕面积、I型胶原蛋白含量和血浆BNP浓度降低（<0.01）。
外源性给予PlGF可刺激血管生成并改善心脏功能。L-精氨酸可增加eNOS蛋白的表达。与单独外源性PlGF治疗相比，PlGF和L-精氨酸对心肌保护具有更显著的协同保护作用。
