胸腺素β4对大鼠急性心肌梗死后心功能的影响

目的探讨慢病毒介导的胸腺肽β4基因经梗死区直接注射对大鼠急性心肌梗死后心功能的影响。方法雄性SD大鼠32只,随机分为4组,每组8只。假手术组:开胸+不结扎冠状动脉,心肌内分五点注射生理盐水50μl;生理盐水组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射等量生理盐水50μl;胸腺肽β4组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射pGC-FU-胸腺肽β4 50μl;空载病毒组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射空载病毒50μl。4周后,大鼠心脏超声测定心功能,Western blot法检测胸腺肽β4和血管内皮生长因子蛋白的表达,RT-PCR法检测胸腺肽β4基因的表达。结果胸腺肽β4组LVEF较生理盐水组和空载病毒组明显提高(P<0.01)。胸腺肽β4组心肌组织中胸腺肽β4和血管内皮生长因子蛋白表达较假手术组、生理盐水组和空载病毒组明显增加,差异有统计学意义(P<0.05)。结论经梗死区直接注射慢病毒载体携带的胸腺肽β4基因可以改善心肌梗死后的心功能。     

内皮祖细胞移植治疗大鼠急性心肌梗死的实验研究

目的探讨大鼠内皮祖细胞(EPCs)移植于梗死心肌的增殖分化情况及对心功能的影响。方法分离培养大鼠EPCs,免疫荧光法检测其CD34+、CD133+和Flk-1+的表达。将SD大鼠冠状动脉左前降支结扎制造急性心肌梗死模型后,在梗死心肌处植入DAPI标记的EPCs(实验组)或M 199培养液(对照组)。移植后1周及4周,心脏超声检查心功能,并对梗死区心肌组织进行移植细胞形态学检查及毛细血管密度测定,逆转录聚合酶链反应及酶联免疫吸附测定梗死周边区血管内皮生长因子(VEGF)的表达。结果培养获得EPCs,其表型为CD34+、CD133+和Flk-1+。植入梗死区的EPCs可以分化为血管内皮细胞,实验组梗死心肌处血管密度较对照组明显增高(P<0.01),并且VEGF基因及蛋白表达在移植后1周均较对照组明显增高(P<0.01)。移植后4周,实验组大鼠左心室射血分数及左心室短轴缩短率较对照组明显提高(P<0.01);而移植后1周,两组大鼠超声检测心功能各指标变化不明显。结论同种异体EPCs移植到梗死心肌大鼠缺血心肌能分化为毛细血管内皮细胞,促进梗死后心肌血管新生,改善心功能。     

超声下观察芎芍胶囊对心肌梗死大鼠缺血心肌血管新生的作用

目的探讨中成药芎芍胶囊对心肌梗死大鼠缺血心肌血管新生作用。方法采用开胸冠状动脉左前降支的方法建立心肌梗死模型,清洁级(或SPF级)SD大鼠32只(雄性)分为空白组、模型组、芎芍组、丹参组,每组8只,分别用生理盐水、芎芍胶囊、丹参粉末进行灌胃给药,连续给药。6周后采集数据分离样本,通过二维超声观察大鼠心功能指标,以及大鼠心肌组织中外源性血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)的表达。结果芎芍组、丹参组与模型组比较,左心室收缩末期内径(LVESD)、舒张末期内径(LVEED)、左心室射血分数(LVEF)差异均有统计学意义(P<0.01),芎芍组、丹参组与AMI组比较,VEGF、bFGF差异均有统计学意义(P<0.01)。VEGF、bFGF与LVEF呈正相关(r值分别为0.813、0.589,P<0.01)。结论芎芍胶囊较丹参更具有促进心肌梗死大鼠缺血心肌血管新生,提高心肌梗死大鼠心功能,保护心肌缺血性损伤的作用。     

丹参注射液对内皮祖细胞移植治疗大鼠心肌梗死的效应

目的探讨丹参注射液对外周血内皮祖细胞(EPCs)移植治疗大鼠急性心肌梗死后增殖分化及心功能的影响。方法 88只SD大鼠经冠状动脉左前降支结扎制造急性心肌梗死模型,随机分为心肌梗死对照组(组Ⅰ)、EPCs移植组(组Ⅱ)、丹参注射液治疗组(组Ⅲ)、EPCs移植联合丹参注射液治疗组(组Ⅳ),每组22只。复苏及培养扩增大鼠EPCs(CM-Dil标记),组Ⅱ及组Ⅳ尾静脉注射3×106个/L EPCs,组Ⅲ及组Ⅳ腹腔注射丹参注射液0. 5 g·kg~(-1)·d~(-1),连续移植及药物治疗3 d。移植后3 w及6 w超声心动图检测心功能,移植后6 w对梗死区心肌组织进行毛细血管密度测定。荧光显微镜观察心肌内移植EPCs及心肌修复情况(苏木素-伊红染色),RT-PCR检测各组心肌血管内皮生长因子(VEGF)基因表达,Western印迹法检测各组心肌中VEGF蛋白表达。结果细胞移植3 w及6 w后,组Ⅱ、组Ⅲ和组Ⅳ左室收缩舒张功能较组Ⅰ明显改善(P<0. 05),且组Ⅳ改变更显著(P<0. 01);组Ⅳ植入梗死区的EPCs可以分化为血管内皮细胞,组Ⅳ梗死心肌处血管密度较组Ⅱ明显增高(P<0. 01); VEGF基因及蛋白表达:组Ⅳ>组Ⅱ>组Ⅲ>组Ⅰ; CM-Dil标记阳性EPCs:组Ⅳ>组Ⅱ,组Ⅲ和组Ⅰ未见CM-Dil标记阳性EPCs;心肌修复情况:组Ⅳ>组Ⅱ、组Ⅲ>组Ⅰ。结论外周血EPCs移植可显著改善急性心肌梗死大鼠的心功能,EPCs移植同时予以丹参注射液优于单独应用EPCs移植,起到心肌修复的协同作用。     

养心通脉方含药血清预处理内皮祖细胞对急性心肌梗死兔心肌bFGF、VEGF水平的影响

目的观察养心通脉方含药血清预处理内皮祖细胞(EPCs)对急性心肌梗死(AMI)兔心肌血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)水平的影响。方法从35只雄性SPF级兔中随机选取25只建立急性心肌梗死兔模型,随机分为模型组、中药EPCs心肌注射组、中药EPCs耳缘静脉注射组、EPCs心肌注射组、EPCs耳缘静脉注射组,每组5只,另设正常组和假手术组,各5只,通过移植干预后14 d取梗死心肌区及缺血心肌区组织,荧光定量聚合酶链式反应(PCR)检测bFGF、VEGF的mRNA表达,蛋白质印迹法(Western Blot)检测bFGF、VEGF蛋白表达。结果在梗死心肌区及缺血心肌区,中药EPCs心肌注射组和中药EPCs耳缘静脉注射组bFGF、VEGF的mRNA及蛋白表达明显高于假手术组、模型组、EPCs心肌注射组、EPCs耳缘静脉注射组,差异均有统计学意义(P<0.05),但中药EPCs心肌注射组bFGF、VEGF的mRNA及蛋白表达与中药EPCs耳缘静脉注射组比较差异均无统计学意义(P>0.05),EPCs心肌注射组bFGF、VEGF的mRNA及蛋白表达与EPCs耳缘静脉注射组比较差异均无统计学意义(P>0.05)。结论养心通脉方含药血清预处理EPCs,能够明显增加损伤心肌bFGF、VEGF表达,但耳缘静脉注射与心肌注射疗效相当。     

远志皂苷元对内皮祖细胞移植治疗急性心肌梗死模型大鼠心功能的影响

目的探讨远志皂苷元对外周血内皮祖细胞(EPCs)移植治疗急性心肌梗死大鼠后心功能的影响。方法80只SD雄性大鼠,将冠状动脉左前降支结扎制造急性心肌梗死模型后,随机分为四组:心肌梗死对照组(组Ⅰ)、远志皂苷元治疗组(组Ⅱ)、EPCs移植组(组Ⅲ)、EPCs移植联合远志皂苷元治疗组(组Ⅳ),每组20只。复苏及培养扩增大鼠外周血EPCs(CM-Dil标记)后,移植到大鼠(组Ⅲ及组Ⅳ)急性心肌梗死模型梗死区,组Ⅱ及组Ⅳ尾静脉注射注远志皂苷元30 mg/kg(30 mg远志皂苷元溶于10 ml生理盐水),连续治疗3 d。移植后3 w及6 w,超声心动图检测大鼠心功能改变,并对梗死区心肌组织进行毛细血管密度测定,逆转录聚合酶链反应及酶联免疫吸附法测定梗死周边区血管内皮生长因子(VEGF)的表达。荧光显微镜下观察心肌梗死部位内移植的EPCs(CM-Dil标记)的数量及大鼠心肌恢复状况(HE染色)。结果细胞移植3和6 w后,组Ⅱ、组Ⅲ和组Ⅳ心功能和左室舒缩功能较对照组明显改善(P<0. 05),且组Ⅳ改变更显著(P<0. 05),组Ⅲ和组Ⅳ植入梗死区的EPCs可以分化为血管内皮细胞,组Ⅳ梗死心肌处血管密度较组Ⅲ、组Ⅱ明显增高(P<0. 05); VEGF基因及蛋白表达:组Ⅳ>组Ⅲ>组Ⅱ>组Ⅰ(P<0. 05); CM-Dil标记EPCs阳性细胞:组Ⅳ>组Ⅲ,组Ⅱ和组Ⅰ未见;心肌修复情况:组Ⅳ>组Ⅲ、组Ⅱ>组Ⅰ。结论外周血EPCs移植可以显著改善急性心肌梗死大鼠的心功能,并在EPCs移植同时予以远志皂苷元干预优于单独应用EPCs移植,起到心肌修复的协同作用。     

硝酸异山梨酯对大鼠缺血心肌血管新生的影响

目的观察硝酸异山梨酯对急性心肌梗死(AMI)大鼠缺血心肌组织形态、梗死面积及毛细血管新生的影响。方法Wistar大鼠90只建立AMI模型后,随机分为5组,分别为正常组,假手术组,模型组,硝酸异山梨酯低剂量组(IDL组)和硝酸异山梨酯高剂量组(IDH组),每组18只。大鼠饲养7、14天后各随机处死9只,截取心肌组织,进行光镜、电镜观察,利用NBT染色法测定心肌梗死面积,应用免疫组织化学法测定Ⅷ因子,进而计算缺血心肌微血管密度(MVD),通过RT-PCR技术检测血管内皮生长因子(VEGF)及碱性成纤维细胞生长因子(bFGF)基因表达情况。结果光镜下观察,缺血区可见炎细胞浸润、心肌肿胀、梗死区纤维化。与模型组比较,IDL组和IDH组7、14天心肌梗死面积明显缩小,MVD明显增加(P<0.05);正常组、假手术组VEGF mRNA、bFGF mRNA表达有所减少,而IDH组则有所增加。结论硝酸异山梨酯可明显缩小AMI大鼠梗死面积,促进缺血心肌的毛细血管新生,对心肌缺血损伤具有保护作用。     

血管内皮生长因子基因转染骨髓间充质干细胞移植促进缺血心肌血管生成的研究

目的研究血管内皮生长因子(vascularendothelial growth factor,VEGF)基因转染骨髓间充质干细胞(mesenchymalstem cells,MSCs)移植对缺血心肌的血管生成作用。方法于2004年5月至2005年8月取第四军医大学西京医院分离、培养Wistar大鼠的MSCs,用真核表达载体pcDNA3.1(-)/hVEGF165转染MSCs。45只近交系Wistar大鼠随机均分为转染组(MSCs/VEGF组)、对照组(MSCs组)、无血清培养基组(DMEM组),结扎前降支建立急性心肌梗死模型后在梗死区边缘区行5×106细胞移植,DMEM组行等量培养基注射。细胞移植前行CM-DiI标记。移植1个月后行心脏B超测量射血分数值,组织化学染色评价新生血管密度。结果培养的MSCs呈典型贴壁生长成纤维样外观,pcDNA3.1(-)/hVEGF165能有效转染大鼠MSCs,移植1个月后MSCs/VEGF组较其余各组左室射血分数(LVEF),再生血管密度明显增加,差异均有显著性(P<0.01)。结论VEGF基因转染MSCs移植能显著促进缺血心肌血管再生,进而改善心脏功能。     

利拉鲁肽对急性心肌梗死大鼠血管新生和心肌保护的影响及机制研究

目的:观察利拉鲁肽对急性心肌梗死大鼠心肌血管新生的影响及其心肌保护作用。方法:冠状动脉结扎法建立大鼠急性心肌梗死模型,成功建模的大鼠随机分为三组(每组6只):对照组、利拉鲁肽低剂量组(LS组)和利拉鲁肽高剂量组(HS组),另外取6只大鼠仅穿线,不结扎,作为假手术组。LS组和HS组建模后分别腹腔皮下注射利拉鲁肽70μg/(kg·d)和140μg/(kg·d),假手术组和对照组均注射相应生理盐水,每天1次,共2周。4周后,超声心动图评估大鼠心脏结构及功能,HE染色观察心肌组织形态学变化,Masson染色计算胶原容积分数(CVF),免疫组织化学法检测大鼠心肌梗死边缘区微血管密度(MVD)及血管内皮生长因子(VEGF)蛋白表达,蛋白免疫印迹(Western blot)法检测VEGF蛋白含量。结果:4周后,对照组较假手术组左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)均明显减低,左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)及CVF明显增加(P均0.01),而MVD及VEGF蛋白水平差异无统计学意义(P0.05);与对照组相比,LS组和HS组LVEF、LVFS明显升高(P0.01),LVEDd、LVESd降低(P0.05),CVF明显下降(P0.01),MVD及VEGF蛋白水平显著增加(P0.01);HS组较LS组LVEF、LVFS明显升高(P0.01),LVEDd、LVESd和CVF下降(P0.05),MVD及VEGF蛋白水平增加(P0.01或P0.05)。结论:利拉鲁肽可促进急性心肌梗死大鼠血管新生,可能与增加VEGF蛋白表达有关,并可减少胶原沉积,从而改善左心室收缩功能,发挥心肌保护作用,且与剂量有一定关系。     

VEGF在大鼠心肌梗死急性期表达的意义及蜕皮甾酮的促侧支循环作用

目的以急性心肌梗死大鼠为模型,观察血管内皮生长因子(VEGF)在心肌中的表达,探讨急性缺血缺氧刺激与VEGF产生的关系和意义以及蜕皮甾酮(EDS ecdysterone)的促侧支循环作用.方法建立Wistar大鼠急性心肌梗死模型,分为对照组、急性心肌梗死组(1、3、7 d)和蜕皮甾酮干预治疗组(每只0,40mg/d).免疫组化检测VEGF表达;Ⅷ因子相关抗原标记内皮细胞,检测毛细血管密度,比重法测定梗死面积.原代培养大鼠心肌细胞,在常氧与缺氧状态下实验组分别给于蜕皮甾酮治疗(100μg/ml),24h后采用免疫细胞化学法检测心肌细胞中VEGF表达.结果随缺血缺氧时间的延长心肌产生的VEGF增加,与对照组比较各组均有显著差异,缺血时间与VEGF产生量呈正相关;蜕皮甾酮治疗组与对照组相比,血清肌酸激酶同功酶(CK-MB)显著降低(P＜0.01);毛细血管密度增加(P＜0.01);心肌梗死面积减少(P＜0.01).在常氧与缺氧状态下,蜕皮甾酮治疗组心肌细胞VEGF表达显著高于对照组(P＜0.01).结论在心肌梗死急性期缺血心肌通过分泌VEGF对自身产生重要的保护作用;蜕皮甾酮进一步刺激心肌分泌产生VEGF,促进大鼠缺血区血管生成、侧支循环建立、毛细血管密度增加,发挥心肌保护作用.     

Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis

BACKGROUND: Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. AIM: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. METHODS: Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection. RESULTS: Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P<0.05 to 0.01). Apoptotic index in the treated group was less than in the control (P<0.01). Caspase-3 activation and mitochondrial cytochrome c release in the treated group were also lower than in the control (P<0.01). VEGF165 cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium. CONCLUSION: Intramyocardial injection of VEGF165 cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction.     

Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction

BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.     

Intramyocardial delivery of VEGF<Subscript>165</Subscript> via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction

Vascular endothelial growth factor (VEGF), an independent mitogen, has been reported to induce angiogenesis and thus attenuates the damage induced by myocardial infarction (MI). VEGF₁₆₅ is the most abundant and predominant isoform of VEGF. This study investigates whether this effect could be strengthened by local intramyocardial injection of VEGF₁₆₅ along with a novel biodegradable Dex-PCL-HEMA/PNIPAAm hydrogel and ascertains its possible mechanism of action. Rat models of myocardial infarction were induced by coronary artery ligation. Phosphate-buffered saline (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), phosphate-buffered saline containing VEGF₁₆₅ (VP group), and hydrogel containing VEGF₁₆₅ (VPG group) were injected into a peri-infarcted area of cardiac tissue immediately after myocardial infarction, respectively. The sham group was thoracic but without myocardial infarction. The injection of VEGF₁₆₅ along with a hydrogel induced angiogenesis, reduced collagen content and MI area, inhibited cell apoptosis, increased the level of VEGF₁₆₅ protein and the expression of flk-1 and flt-1, and improved cardiac function compared with the injection of either alone after MI in rats. The results suggest that injection of VEGF₁₆₅ along with a hydrogel acquires more cardioprotective effects than either alone in rat with MI by sustained release of VEGF₁₆₅, then may enhance the feedback between VEGF and its receptors flk-1 and flt-1.     

Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation

OBJECTIVES: The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF165) in the border zone of myocardial infarct tissue in rat hearts were investigated. BACKGROUND: Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium. METHODS: Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 +/- 6.5 days, the rats were injected with phVEGF165 at one location and control plasmid at a second location (500 microg DNA, n = 24) or saline (n = 16). After 33.1 +/- 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres. RESULTS: phVEGF165-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF165-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF165-treated hearts revealed 44.4 +/- 10.5 vascular structures per field in phVEGF165-treated hearts versus 21.4 +/- 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF,165-treated hearts (0.9 +/- 0.2) and saline-treated hearts (0.7 +/- 0.1). CONCLUSIONS: Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.     

激光心肌血运重建术与VEGF基因治疗犬心肌缺血心功能的变化

目的　观察 TML R联合 VEGF1 65c DNA治疗心肌缺血犬后心功能的变化。方法　健康杂种犬 36只 ,随机分为 VEGF1 65基因组、空质粒组 ,激光心肌打孔为对照组 (n=12 ) ,结扎冠状动脉造成急性心肌缺血后 6 0 min分别行CO2 激光心肌打孔和基因转染。采用热稀释法和彩色多谱勒超声心动图检测心排量 (CO)和左心室射血分数(L VEF)。结果　治疗后 6周和 12周 VEGF1 65c DNA组 L VEF和 CO显著高于激光打孔组 (P<0 .0 5 ) ,以治疗后 12周最为显著。结论　犬急性心肌缺血后采用激光心肌打孔联合 VEGF1 65基因治疗可显著改善心功能。     

心肌内注射17β-雌二醇纳米粒对大鼠心肌梗死影响的研究

目的探讨心肌内局部注射17β-雌二醇纳米粒对大鼠心肌梗死后血管生成、梗死面积、死亡率的影响。方法以聚乳酸和乙醇酸共聚物(PLGA)纳米粒为载体制备17β-雌二醇纳米粒,评价其理化性质及体内、体外药物释放参数。将75只SD雌鼠制备去卵巢心肌梗死模型,制模成功60只大鼠随机分为实验组(梗死边缘区注射17β-雌二醇纳米粒4mg/100g)、实验对照组(梗死边缘区注射空白纳米粒4mg/100g)和空白对照组(仅制备去卵巢心肌梗死模型),每组20只。1个月后免疫组织化学法检测心肌梗死边缘区毛细血管密度(MVD)及内皮型一氧化氮合酶(eNOS)累积吸光度(A)值,并测量梗死面积。结果17β-雌二醇从PLGA纳米粒载体中缓慢释放1个月,与空白对照组和实验对照组比较,实验组心肌梗死1个月后梗死边缘区MVD增加(P<0.05),eNOSA值增多(P<0.05),梗死面积减小(P<0.05),死亡率无升高(P=1.000)。结论心肌内局部注射17β-雌二醇纳米粒可以促使大鼠心肌梗死后心肌毛细血管生成,减少心肌梗死面积,不增加死亡率。     

腺相关病毒介导的PR39联合ADM基因表达产物防治大鼠心肌梗死的研究

目的 探讨以腺相关病毒（adeno-associated virus,AAV）作为载体的抗菌肽PR39与肾上腺髓质素（adrenomendullin,ADM）双基因共表达产物（rAAV-PR39-ADM）对大鼠心肌梗死的防治作用。方法 冠状动脉左前降支结扎建立心肌梗死（myocardial infarction,MI）模型。将雄性SD大鼠分为Sham组（假手术），生理盐水组（MI+NS），空病毒组（MI+AAV-GFP）和治疗组（MI+rAAV-PR39-ADM）。各组大鼠手术4周后行B型超声、血流动力学检测心功能，心脏病理染色计算梗死面积和胶原容积分数，免疫荧光检测可以间接代表PR39和ADM表达的标签肽6His-Tag，Western blot检测6His标签肽以及血管内皮生长因子 (vascular endothelial growth factor,VEGF)蛋白表达。结果 B超及血流动力学指标显示治疗组射血分数（ejection fraction,EF）和各项心功能指标较生理盐水与空病毒组明显改善，MI面积明显减小（P<0.05）；且标签肽以及VEGF蛋白表达量高于空病毒组与生理盐水组（P<0.05）。结论 rAAV-PR39-ADM具有明显改善MI大鼠的心脏功能、减少MI面积，促进血管生成的作用。     

重组中期因子对大鼠心肌梗死后心室重塑及Ⅲ型前胶原氨基端肽的影响

目的研究早期应用中期因子（MDK）对大鼠心肌梗死后心室重塑的作用及对Ⅲ型前胶原氨基端肽（PⅢNP）与心功能的影响。方法结扎Wistar大鼠左冠状动脉前降支建立心肌梗死动物模型。32只大鼠随机分为3组：对照组（Sham,8只）、心肌梗死组（MI,12只）和心肌梗死＋人重组中期因子干预组（MI＋MDK,12只）。造模成功后1μg／200g人重组中期因子在梗死周围分5点注射给药。4周后,所有大鼠行血流动力学、PⅢNP、微血管、胶原的测定及心脏标本的病理学分析。结果与MI组比较,MI＋MDK组的SBP、MAP、LVSP和±dp／dtmax显著增高,而LVEDP显著降低（P〈0．01）;血清PⅢNP值显著增加（P〈0．01）。病理标本分析：与MI组相比,MI＋MDK组梗死区中胶原容积分数显著增加,非梗死区中显著减少;MI＋MDK组有更多新生血管出现（P〈0．05）;MI＋MDK组炎细胞浸润、梗死面积、心肌肥大程度、心室重量明显减轻（P〈0．01）。结论急性心肌梗死大鼠早期应用MDK能发挥血管形成和胶原刺激的作用,对延缓急性心肌梗死后心室重塑发挥重要的作用。     

穿心室壁内支架联合血管内皮生长因子治疗急性心肌梗死的研究

目的 确定穿心室壁内支架联合血管内皮生长因子基因治疗在猪急性心肌梗死（AMI）模型中的治疗作用。方法 中国小型猪30头随机分为四组：心肌梗死组（MI）;支架组（ST）;内皮生长因子基因组（VEGF）和支架＋基因组（ST＋VEGF）。MI组采用结扎冠状动脉左前降支形成AMI模型,其余三组在形成梗死模型后分别采用穿心室壁支架置入、直接心肌内注射携带hVEGF165的质粒载体以及联合治疗。4周后行心脏超声、心肌血管密度检测和免疫组化等检查。结果 4周后ST组、VEGF组、ST＋VEGF组的血管密度均明显多于MI组,其中ST＋VEGF组与其他各组比较在促进血管生长方面有明显优势（P〈0．01）。VEGF组和ST＋VEGF组较MI组在VEGF蛋白表达方面明显提高。结论 穿心室壁内支架联合VEGF治疗综合了支架形成通道、机械刺激促进血管生成以及携带促血管生成因子基因的载体的输送作用,提供了一种比任何单独治疗心肌梗死技术更有效的手段。     

急性心肌梗死时G-CSF的抗心肌重构及对心功能改善的实验研究

目的探讨急性心肌梗死（AM I）时动员剂粒细胞集落刺激因子（G ranu locyte colony-stimu lating factor,G-CSF）抗心肌重构和功能保护作用。方法日本大耳白兔40只,随机分成两组,每组20只,均结扎冠状动脉前降支建立心肌梗死模型,动员剂组于模型建立后1 h给予G-CSF皮下注射连续7 d,对照组系建立心肌梗死模型后仅注射生理盐水。术前、术后24 h及术后4周做心脏超声检测心功能,4周后处死动物,取出心脏行组织病理学分析,测定两组梗死面积的大小、毛细血管密度以及观察纤维化的情况。结果动员剂组心功能各项指标在术后4周时均较对照组有明显的改善。HE染色显示对照组心肌纤维排列紊乱不规则,而动员剂组排列有序,梗死灶较对照组明显减小,且毛细血管密度也显著增加。胶原纤维明显少于对照组。结论急性心肌梗死时给予G-CSF可有效增加梗死区及周围毛细血管密度,缩小梗死面积,稳定心脏结构及显著改善心功能。