中文摘要：

目的探索腺病毒介导的鞘氨醇激酶1（SPK1）基因局部表达对心肌梗死后心衰的治疗作用。方法将20只Wistar大鼠（250～300g）随机分成3组：假手术组（6只）、Ad-GFP对照组（7只）和Ad-SPK1（7只）组。结扎Wistar大鼠冠状动脉左前降支,Ad-SPK1组在心脏梗死区及周围多位点注射携带人SPK1基因的复制缺陷型重组腺病毒（Ad-SPK1）,Ad-GFP对照组注射同体积的携带绿色荧光蛋白（GFP）基因的重组腺病毒（Ad-GFP）,14d后进行血流动力学及组织形态学检查。结果 Ad-SPK1组左心室收缩压（LVSP）、左心室舒张末压（LVEDP）、最大左心室收缩压上升/降低时间（±dP/dtmax）（分别为132.82±13.03mmHg、4.34±0.69mmHg、5095.20±384.79）与Ad-GFP组（分别为76.96±8.44mmHg、14.79±1.08mmHg、2954.12±195.05）比较明显改善（P〈0.01）,而与假手术组（分别为147.42±10.92mmHg、2.80±0.45mmHg、5865.19±484.36）比较则无明显差异。Ad-SPK1组梗死区面积（3.78%±0.96%）与Ad-GFP组（38.86%±5.68%）比较明显减小（P〈0.01）。Ad-SPK1组左心室直径、左心室壁厚度（分别为4.63±0.80mm、2.70±0.29mm）与Ad-GFP组（分别为7.30±1.03mm、1.34±0.36mm）比较,直径明显缩小,厚度变薄的程度减轻（P〈0.01）,而与假手术组（分别为4.50±0.36mm、2.80±0.34mm）比较则无明显差异。Ⅷ因子相关抗原免疫组化分析显示,SPK1基因转染能明显刺激梗死缺血区的血管生成;天狼星红染色结果表明,SPK1基因转染能显著降低胶原在梗死缺血区的沉积。结论腺病毒介导的SPK1基因转染能够保护缺血导致的心功能损伤,局部Ad-SPK1注射可能是治疗缺血性心脏病的一条新途径。

英文摘要：

Objective To investigate the therapeutic effect of adenovirus-mediated sphingosine kinase 1gene（Ad-SPK1）transfection on amelioration of post-infarction heart failure.Methods Twenty Wistar rats（250-300g）were randomized to three groups：sham group （n=6）,adenovirus-mediated green fluorescent protein group（Ad-GFP,n=7）and Ad-SPK1group（n=7）.The left anterior descending branch of coronary artery was ligated,followed by direct intramyocardial injection of AD-SPK1or Ad-GFP gene in multiple sites as control.The hemodynamics and histomorphology of heart was analyzed 14days after operation.Results Left ventricular systolic pressure （LVSP）,left ventricular end-diastolic pressure（LVEDP）and maximum dP/dt in Ad-SPK1group（132.82±13.03mmHg,4.34± 0.69mmHg and 5095.20±384.79,respectively）were significantly improved compared with that in Ad-GFP group（76.96±8.44mmHg, 14.79±1.08mmHg and 2954.12±195.05,respectively,P〈0.01）,but there were no significant differences between Ad-SPK1group and sham group（147.42±10.92mmHg,2.80±0.45mmHg and 5865.19±484.36,respectively）.Infarct size in Ad-SPK1group（3.78%± 0.96%）was significantly smaller than that in Ad-GFP group（38.86%±5.68%,P〈0.01）.Left ventricular（LV）diameter and LV wall thickness in Ad-SPK1group（4.63±0.80mm,2.70±0.29mm,respectively）were significantly smaller than that in Ad-GFP group （7.30±1.03mm,1.34±0.36mm,respectively,P〈0.01）,but no differences were observed between Ad-SPK1group and sham group （4.50±0.36mm,2.80±0.34mm）.Transfection of SPK1gene enhanced angiogenesis significantly as revealed by Von Willebrand’s factor immunohistochemical staining and blood vessel counting,and reduced fibrosis shown by Sirius red staining.Conclusions Transfection of adenovirus-mediated SPK1gene may efficiently improve postischemic heart failure by enhancing angiogenesis and reducing fibrosis, implying that the transfection of adenovirus-mediated SPK1gene might provide a novel strategy for treatment of coronary heart di