血红素氧化酶-1基因修饰的自体骨髓间充质干细胞移植治疗猪急性心肌梗死  

Effects of autologous mesenchymal stem cells transfected with heme oxygenase-1 gene transplantation on ischemic Swine hearts

作　　者：蒋益波[1] 陈立娟[1] 唐耀亮[1] 马根山[1] 祈春梅[1] 朱琪[1] 张晓黎[1] 姚玉宇[1] 刘乃丰[1] 沈成兴[1] 

机构地区：[1]南京东南大学附属中大医院心内科,210009

出　　处：《中华心血管病杂志》2009年第8期692-695,共4页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30670853）

摘　　要：目的研究骨髓间充质干细胞（MSC）经血红素氧化酶-1（HO-1）基因修饰后移植对急性心肌梗死的治疗作用。方法细胞分为3组，未转染质粒组（MSC组）、转染空载质粒组（LacZ—MSC组）、转染pcDNA3．1-hHO—1组（HO-1-MSC组），体外实验予缺氧诱导观察HO-1基因转染后MSC的抗凋亡情况，同时收集上清液检测血管内皮生长因子（VEGF）的表达。体内实验建立猪的急性心肌梗死模型，梗死1h再灌注1h后分为3组，即生理盐水组、单纯干细胞治疗组（MSC组）及HO-1基因转染干细胞治疗组（HO-1-MSC组）。治疗组分别予MSC及HO-1-MSC移植治疗，对照组则注入等量生理盐水。细胞移植后1周及3个月行磁共振检测。3个月后处死动物，取心脏标本行相关检查。结果（1）体外缺氧诱导实验中HO-1-MSC组凋亡率（30．30±7．64）％低于MSC组（56．93±4．68）％（P〈0．001）和LacZ—MSC组（55．88±4．38）％（P〈0．001）。同时上清液中VEGF的分泌HO-1-MSC组（768．44±78．38）pg／ml高于Msc组（555．27±67．67）pg／ml（P〈0．001）和LacZ-MSC组（522．97±71．45）pg／ml（P〈0．001）。（2）细胞移植3个月后HO-1-MSC组LVEF（53．50±2．09）％明显高于MSC组（49．54±2．74）％（P=0．017）。梗死周边区毛细血管密度（血管数／HPF）HO-1-MSC组14．594-2．39亦大于MSC组11．78±2．48（P=0．033）。结论HO-1基因转染MSC较单纯MSC移植治疗急性心肌梗死疗效明显。Objective To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia （ 1 h ）/reperfusion. Methods Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups： control group （saline） , MSCs group （MSCs） , MSCs transfeeted with pcDNA3.1-nHO-1 （HO-1-MSCs） . 1 ×10^7 of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation. Results In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1- MSCs group （30. 30% ±7.64% ） compared with that in MSCs group （56. 93% ±4. 68% , P 〈0. 001 ） and LacZ- MSCs group （ 55.88% ± 4. 38% , P 〈 0. 001 ） , VEGF was also significantly upregulated in HO-1-MSCs group [ （768.44 ± 78.38 ） pg/ml ] compared with that in MSCs group [ （555.27 ± 67. 67 ） pg/ml, P 〈 0. 001 ] and LacZ-MSCs group [ （522. 97 ± 71.45 ） pg/ml, P 〈 0. 001 ] . In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group （all P 〈0. 05 vs. saline） and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation （53. 50% ± 2. 09% vs. 49. 54% ± 2. 74%, P = 0. 017）, capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [（14.59 ± 2.39）/HPF vs. （11.78 ±2.48）/HPF, overexpressed MSCs on improving cardiac function and MSCs in this porcine ischemia/reperfusion model. P = 0. 033 ] . Conclusions Efficacy of HO-1 promoting angiogenesis was greater than those by

关 键 词：心肌梗死 间质干细胞移植 血红素氧化酶-1 

分 类 号：R686[医药卫生—骨科学]