骨髓间充质干细胞介导的血红素氧合酶-1促进大鼠心肌梗死后血管再生  

HO-1 transduced by MSCs promotes angiogenesis in rat infracted myocardium

作　　者：曾彬[1] 王艾力 彭小凡[3] 李昌 

机构地区：[1]武汉大学人民医院心血管内科,湖北武汉430060 [2]中南医院心血管内科超声心动室,湖北武汉430071 [3]武汉大学 [4]湖北省中山医院心内科,湖北武汉430033

出　　处：《基础医学与临床》2014年第2期145-150,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金青年项目(30900609);国家自然科学基金(81270271)

摘　　要：目的探讨骨髓间充质干细胞(MSCs)介导的血红素氧合酶-1(HO-1)对心肌梗死后心脏血管再生及左心室功能的影响。方法取大鼠骨髓,体外分离扩增培养MSCs,HO-1腺病毒转染。结扎左前降支1 h后,分别将HO-1-MSCs、MSCs多点注射到大鼠心肌梗死区周边,对照组注射等量PBS。结果 MSCs介导的HO-1能在体外及体内获得稳定表达;HO-1-MSCs组促血管生长因子VEGF、FGF2的表达及毛细血管密度明显高于MSCs组和对照组(P<0.01);但促血管再生的作用可被HO抑制剂阻断。HO-1-MSCs组心肌细胞凋亡及纤维化明显低于MSCs组和对照组(P<0.01);HO-1-MSCs组左室收缩功能各项指标明显优于其他两组(P<0.01)。HO-1-MSCs组心室壁变厚,心室腔明显缩小。结论 MSCs介导的血红素氧合酶-1能促进心肌梗死后心脏血管再生,改善左心室功能。Objective Heine oxygenase-1 （HO-1） is a stress-inducible enzyme with diverse eytoprotective effects, and plays a role in angiogenesis recently. We investigated whether HO-1 transduced by MSCs can induce angiogen- ic effects in infracted myocardium. Methods Methods HO-1 was transfected into cultured MSCs using an adenovi- ral vector. 1× 10^6 Ad-HO-1-transfected MSCs （HO-1-MSCs） or Ad-Null-transfected MSCs （Null-MSCs） or PBS was respectively injected into rat hearts 1 h intramyocardially after myocardial infarction. Results HO-1-MSCs was able to induce stable expression of HO-1 in vitro and Vivo. The capillary density and expression of angiogenic growth factors, VEGF and FGF2, were significantly enhanced in HO-1-MSCs-treated hearts compared with Null- MSCs-treated and PBS-treated hearts. However, the angiogenic effects of HO-1 in HO-1-MSCs group was abolished by treating the animals with HO inhibitor, zinc protoporphyrin. The myocardial apoptosis was marked reduced with significantly reduced fibrotic area in HO-1-MSCs-treated hearts; Furthermore, the cardiac function and remodeling were also significantly improved in HO-1-MSCs-treated hearts than in the other two groups. Conclusions HO-1modification with MSCs reduces the apoptosis of myocardium and protect cardiac function and remodeling, and that this is associated with siginficant angiogenesis.

关 键 词：骨髓间充质干细胞 心肌梗死 红素氧合酶-1 血管再生 

分 类 号：R542.22[医药卫生—心血管疾病]