肝细胞生长因子治疗心肌梗死后心力衰竭的实验研究Amelioration in cardiac function with Ad5-HGF transference in postinfarction heart failure swine
王伟,杨志健,马东超,徐顺霖,王连生,张郁青,曹克将,马文珠
摘要(Abstract):
目的研究经冠状动脉转染携带人肝细胞生长因子(hepatocytegrowthfactor,HGF)的腺病毒(adenovirus,Ad5)对猪心肌梗死后心力衰竭的改善作用。方法12只苏中幼猪,随机分成转染Ad5-HGF组(治疗组)和转染未携带肝细胞生长因子的腺病毒载体(null-Ad5)组(对照组),每组6只。结扎前降支制成心肌梗死模型,手术后第4周及第7周时行冠状动脉造影和门控心肌灌注显像,评价侧支循环形成程度(Rentorp法)、心肌灌注及心功能的变化;用ELISA法检测肝细胞生长因子蛋白表达;以免疫组织化学法检测基因导入后平滑肌肌动蛋白抗体阳性(SMA+)有灌注功能血管生成情况。结果经冠状动脉转染Ad5-HGF后心肌高度表达人HGF蛋白;治疗组心肌血流灌注及左心室射血分数(LVEF)较对照组明显改善;治疗组侧支循环形成明显增多,每平方毫米功能血管的数量明显高于对照组。结论经冠状动脉转染Ad5-HGF能使心肌高度表达HGF蛋白。HGF对梗死心肌的侧支循环形成、心肌灌注及心功能均有改善作用,能促进功能血管数增多。
关键词(KeyWords): 基因疗法;心力衰竭,充血性;心肌梗死;侧支循环
基金项目(Foundation):
作者(Author): 王伟,杨志健,马东超,徐顺霖,王连生,张郁青,曹克将,马文珠
参考文献(References):
- [1]Fliss,H,Gattinger D.Apoptosis in ischemic and reperfused rat myocardium.Circ Res,1996,79:949-956.
- [2]SalamAM.Selective aldosterone blockade witheplerenonein patients with congestive heart failure.Expert Opin Invest Drugs,2003,12:1423-1427.
- [3]Rentrop KP,Cohen M,Blanke H,et al.Change in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects.J Am Coll Cardial,1985,5:587-592.
- [4]White FC,Carroll SM,Magnet A,et al.Coronary collateral development in swine after coronary artery occlusion.Circ Res,1992,71:1490-1500.
- [5]Tomita N,Morishiea R,Taniyama Y,et al.Angiogenic property of hepatocyte growth factor is dependent on upregulation of essential transcriptionfactor for angiogenesis,ets-1.Circulation,2003,107:1411-1417.
- [6]FamNP,Verma S,Kutryk M,et al.Clinician guide to angiogenesis circulation.2003,108:2613-2618.
- [7]Schwartz RY.Kornowski progenitor and embryonic stem cell transplantationfor myocardial angiogenesis and functional restoration Eur Heart J,2003,24:404-411.
- [8]吴丹莉,劳妙芬,邱兆华,等.腺病毒载体介导肝细胞生长因子基因对大鼠心肌缺血的基因治疗.科学通报,2002,47:1726-1729.