摘要:
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-Dawtey 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/mm2 vs 34.8/mm2,P<0.01) and α-SMA positive microvessels of the peri-infarct area (20.2/mm2 vs 7.2/mm2,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.%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/mm2比34.8/mm2,P<0.01),α-SMA阳性平滑肌细胞密度亦高于对照组(20.2/mm2比7.2/mm2,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.