目的:探讨携带人血管内皮生长因子165（vascular endothelial growth factor 165, VEGFn 165）的重组腺病毒（Ad-hVEGFn 165）和携带人组织基质金属蛋白酶抑制剂1（tissue inhibitor of metalloproteinase 1, TIMP-1）的重组腺病毒（Ad-hTIMP-1）对心肌梗死大鼠的作用及可能机制。n 方法:健康雄性清洁级8周龄Wistar大鼠30只，采用随机数字表法随机分为5组，假手术组（Sham），空载病毒对照组（Ad-Track），Ad-hVEGFn 165组，Ad-hTIMP-1和双基因组（hVEGFn 165+hTIMP-1），每组6只。除Sham组外，各组大鼠均结扎冠状动脉左前降支建立心肌梗死模型，以心电图出现ST段弓背抬高，Q波或T波倒置，局部心肌变白为模型成功。分别在心肌梗死区域四点注射相应重组腺病毒病毒生理盐水稀释液100 μL（1×10n 10 VP/100 μL）；Sham组未予任何处理。4周后实验动物完成超声心动图检测后处死取心脏组织。免疫组织化学检测大鼠心肌组织hVEGFn 165和hTIMP-1基因表达；实时荧光定量PCR检测各组大鼠心肌组织凋亡相关因子mRNA表达；免疫组织化学检测各组大鼠心肌组织凋亡相关因子蛋白表达。正态分布计量资料多组间均数比较采用单因素方差分析，组间两两比较采用LSD-n t检验。n 结果:超声心动图检测结果显示：Ad-Track组心率（heart rate，HR）（480.83±24.09）次/min、左室舒张末径（left ventricular end-diastolic dimension，LVEDD）（6.88±0.44）mm、左室收缩末径（left ventricular end-systolic dimension，LVESD）（4.85±0.42）mm均较Sham组（433.16±17.86)次/min、（6.20±0.45）mm、（4.06±0.70），增加（n P<0.05），左室射血分数（left ventricular ejection fraction，LVEF）（62.70±3.17）、左室短轴缩短率（left ventricular fractional shortening，LVFS）（29.52±1.88）%均较Sham组（72.78±5.44）%、（37.20±4.71）%显著降低（n P<0.01）；hVEGFn 165-hTIMP-1组LVEF（71.50±6.23）%、LVFS（36.17±5.27）%均显著高于Ad-Track组（n P<0.01），LVEDD（6.22±0.39）mm、LVESD（4.13±0.23）mm均低于Ad-Track组（n P<0.05）；hVEGFn 165-hTIMP-1组LVEF、LVFS均高于Ad-hVEGFn 165组（64.65±4.00）%、（30.95±2.57）%（n P<0.05）。实时荧光定量PCR结果显示：hVEGFn 165-hTIMP-1组心肌组织Bcl-2相关X蛋白（Bax）、半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）、Bal-xl/Bcl-2相关死亡促进因子（Bad）mRNA表达均较Ad-Track组降低（n P<0.01或n P<0.05），B细胞淋巴瘤/白血病-2（Bcl-2）mRNA表达均较Ad-Track组升高（n P<0.01）；hVEGFn 165-hTIMP-1组心肌组织Bax、Caspase-3 mRNA表达较Ad-hVEGFn 165组降低（n P0.05）。免疫组织化学结果显示：hVEGFn 165-hTIMP-1组Bax和Caspase-3蛋白表达较Ad-hVEGFn 165组、Ad-hTIMP-1组及Ad-Track组显著降低（均n P<0.01），Bcl-2蛋白表达较Ad-hVEGFn 165组、Ad-hTIMP-1组及Ad-Track组升高（均n P0.05）。n 结论:联合hVEGFn 165和hTIMP-1基因过表达可改善大鼠心肌梗死后心脏收缩功能，其机制可能与抑制心肌细胞凋亡相关，且hVEGFn 165和hTIMP-1联合可能具有协同作用。n “,”Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGFn 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism.n Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGFn 165 group, Ad-hTIMP-1 group and Ad-hVEGFn 165+Ad-hTIMP-1 group (hVEGFn 165+hTIMP-1) (n n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 n 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF n 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference n t-test.n Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all n P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both n P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGFn 165-hTIMP-1 group were significantly increased (both n P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both n P<0.05). LVEF and LVFS in the hVEGFn 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGFn 165 group (64.65±4.00) %, (30.95±2.57) % (both n P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGFn 165-hTIMP-1 group were decreased than those in the Ad-Track group (n P<0.01 or n P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGFn 165-hTIMP-1 group were increased than those in the Ad-Track group (n P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGFn 165-hTIMP-1 group were decreased than those in the Ad-hVEGFn 165 group (both n P0.05). The protein expression of Bax and Caspase-3 in the hVEGFn 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGFn 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all n P<0.01), and the protein expression of Bcl-2 in the hVEGFn 165-hTIMP-1 group was increased than those in the Ad-hVEGFn 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all n P0.05).n Conclusions:Ad-hVEGFn 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGFn 165 and hTIMP-1 may have a synergistic effect on MI.n