【摘要】 目的 观察左旋精氨酸干预对急性心肌梗死(AMI)大鼠心肌梗死边缘区血管新生的影响及心肌保护作用。方法 冠状动脉结扎法建立大鼠AMI模型,30只SD雄性大鼠被随机分为3组:假手术组、生理盐水对照组及左旋精氨酸干预组。在冠状动脉结扎后4周,超声心动图测量大鼠心脏左室舒张末内径(LVEDD)、左室收缩末内径(LVESD)、左室射血分数(LVEF)、左室短缩分数(LVFS),Masson染色测定梗死面积,ELISA法检测各组大鼠血浆脑钠尿肽(BNP)水平;采用免疫组织化学技术检测大鼠心肌梗死边缘区CD31阳性的内皮细胞数量及α-SMA阳性平滑肌细胞数量,以评估新生血管情况,Western blot检测梗死边缘区内皮型一氧化氮合成酶(eNOS)及胶原-I蛋白含量。结果 冠状动脉结扎术后4周,与生理盐水对照组相比,左旋精氨酸干预组LVEF(48.20%比35.20%,P<0.01)、LVFS(24.10%比17.38%,P<0.01)明显升高,而LVEDD(7.82 mm比9.06 mm,P<0.01)及LVESD(6.29 mm比7.32 mm,P<0.01)降低;梗死面积明显缩小(25.11%比35.02%,P<0.01);血浆BNP水平亦较低(872.33 pg/ml比1203 pg/ml,P<0.01);而梗死边缘区CD31阳性的内皮细胞高于生理盐水对照组(101.4/mm~2比34.8/mm~2,P<0.01),α-SMA阳性平滑肌细胞密度亦高于对照组(20.2/mm~2比7.2/mm~2,P<0.01);梗死周围区eNOS蛋白水平高于对照组,而胶原-I蛋白含量则低于对照组(P<0.01)。结论 左旋精氨酸干预可促进AMI大鼠梗死心肌边缘区毛细血管及小动脉新生,减少胶原-1蛋白含量,促进eNOS的表达,并具有改善左心收缩功能、降低血浆BNP水平、缩小梗死面积的心肌保护作用。更多还原

【Abstract】 Objective To investigate the effect of angiogenesis in peri-infarct area of the L-Arginine therapy for acute myocardial infarction rats and its cardioprotective activity. Methods The AMI rat model was established by ligation of the left anterior descending of coronary arteries. Thirty male Sprague-Dawley rats were randomly divided into three groups: sham group, normal saline group(control group) and L-Arginine group. Four weeks after ligation and treatment, cardiac function, scar area, plasma concentration of BNP, angiogenesis and arteriogenesis, myocardial collagen Ⅰ protein expression were studied. Echocardiography, Masson staining, enzyme-linked immunosorbent assay, immunehistochemistry,western blot were performed. Results Four weeks after ligation, compared with the control group, LVEF(48.20% vs 35.20%, P<0.01), LVFS(24.10% vs 17.38%, P<0.01) were higher in L-Arginine group, while LVEDD(7.82 mm vs 9.06 mm, P<0.01) and LVESD(6.29 mm vs 7.32 mm, P<0.01)decreased obviously. Average scar percentage and plasma concentration of BNP were lower in L-Arginine group(872.33 pg/ml vs 1203 pg/ml, P<0.01). The mean CD31-positive microvessels(101.4/mm~2 vs 34.8/mm~2, P<0.01) and a-SMA positive microvessels of the peri-infarct area(20.2/mm~2 vs 7.2/mm~2, P<0.01)were higher in L-Arginine group, while collagen Ⅰ protein content was decreased in this group(P<0.01).Conclusion L-Arginine intervention improves cardiac function and reduces infarction size in AMI rats, the possible mechanism is related to dual function of promoting angiogenesis and arteriogenesis, reducing collagen Ⅰ expression is also one of the important mechanisms.更多还原