血管内皮生长因子与胎盘生长因子联合对大鼠急性心肌梗死后血管新生及心功能的影响

摘要

Objective To evaluate the combined effects of vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) on angiogenesis and cardiac function and compare with VEGF or PLGF only in acute myocardial infarction rats.Methods Seventy-five males Sprague-Dawley(SD) rats were randomly divided into five groups:sham group,NS group,VEGF group,PLGF group,and VEGF + PLGF group with 15 rats in each group.All the rats underwent LAD ligation and injection of NS,VEGF,PLGF,VEGF + PLGF,in the peri-infarct area,respectively,besides the sham group.Three weeks after coronary artery ligation and different agents injection,cardiac function,myocardial scar area,angiogenesis and arteriogenesis were studied.Cardiac structure and function,and infarct size were assessed by echocardiography.The number of new vessels and the number of new arterioles were evaluated by haematoxylin-eosin staining and immunohistochemistry staining.Results Three weeks after LAD ligation and different agents injection,the LVEDD and LVESD were significantly decreased (P ＜ 0.01)in NS group,VEGF group and PLGF group.While the LVEF and LVFS were higher in VEGF + PLGF group than that in other groups.Myocardial infarct size was reduced in VEGF group (P ＜ 0.05).Angiogenesis and arteriogenesis were higher in VEGF + PLGF group than that in VEGF group (P ＜ 0.01) and PLGF group (P ＜0.05).Angiogenesis and arteriogenesis were significantly higher in PLGF group than that in VEGF group (P＜0.01).The density of microvessels in VEGF group was higher than that in NS group (P ＜ 0.05),while arteriogenesis was of no statistical difference.Conclusion The combination of half VEGF and PLGF can increase angiogenesis and arteriogenesis in the ischemic marginal zone of myocardial infarction,decrease myocardial infarction area,and improve cardiac function.%目的 观察血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)单独使用和联合使用对急性心肌梗死大鼠心肌梗死缺血边缘区血管新生和心功能的影响.方法 75只雄性SD大鼠随机分为5组:sham组(假手术组),NS组(250μl生理盐水),VEGF组(1μg重组鼠VEGF溶于250μl生理盐水),PLGF组(1μg重组鼠PLGF溶于250μl生理盐水),VEGF +PLGF组(重组鼠VEGF0.5 μg+重组鼠PLGF 0.5μg溶于250μl生理盐水).sham组大鼠仅开胸,不结扎左前降支,并且不注射药物,其余所有大鼠均结扎左前降支近端,建立急性心肌梗死模型,并于心肌梗死缺血边缘区注射VEGF和PLGF.术后3周,以超声心动图评估大鼠心脏结构及功能,测定梗死范围,用免疫组织化学方法检测大鼠心肌梗死缺血边缘区Ⅷ因子相关抗原(vWF)染色阳性的内皮细胞评估新生血管数量,α平滑肌肌动蛋白(α-SMA)染色阳性的平滑肌细胞评估新生小动脉数量.结果 冠状动脉结扎3周后,sham组大鼠LVEDD、LVESD、LVEF及LVFS明显优于其余各组,差异均有统计意义(均P＜0.01);与NS组、VEGF组及PLGF组比较,VEGF+ PLGF组LVEF、LVFS显著增高,而LVEDD及LVESD则显著减少(均P＜0.05).sham组心肌梗死范围显著小于其余四组,差异均有统计意义(均P＜0.01);VEGF+ PLGF组大鼠梗死范围显著小于NS组[(19.75±3.98)％比(38.70±7.45)％,P＜0.01]、VEGF组[(19.75±3.98)％比(32.20±6.00)％,P＜0.05]及PLGF组[(19.75±3.98)％比(25.09±5.52)％,P＜0.05],差异均有统计学意义.sham组vWF阳性细胞数量和α-SMA阳性细胞数量显著小于其余四组,差异均有统计学意义(均P＜0.01);其余四组大鼠vWF阳性细胞数量和α-SMA阳性细胞数量比较,差异均有统计学意义(均P＜0.05);而VEGF+PLGF组vWF阳性细胞数量[(64.08±10.89)个/mm2比(55.09 ±8.20)个/mm2,P＜0.05]、α-SMA阳性细胞数量[(11.42±3.15)个/mm2比(9.00±2.19)个/mm2,P＜0.05]均高于PLGF组,差异均有统计学意义.结论 将半剂量的VEGF与PLGF联合应用可使心肌梗死缺血边缘区毛细血管和小动脉生成增多,心肌梗死范围减小,并且明显改善心功能.