转染人血管内皮生长因子165基因的骨髓间充质干细胞移植改善兔心肌梗死后心功能  

Bone Marrow Mesenchymal Stem Cell Transplantation Combined with Vascular Endothelial Growth Factor 165 Gene Transfection Improved Heart Function After Myocardial Infarction in Rabbits

作　　者：盛小刚[1] 宋卉[2] 冯建章[3] 陈秋雄[1] 吴书林[3] 

机构地区：[1]广东省中医院心脏中心,广东省广州市510105 [2]汕头大学医学院药理学教研室,广东省汕头市515031 [3]广东省心血管病研究所,广东省广州市510080

出　　处：《中国动脉硬化杂志》2006年第8期669-672,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的探讨将骨髓间充质干细胞移植和血管内皮生长因子基因治疗相结合治疗兔心肌梗死的疗效及其机制。方法将48只新西兰大白兔随机分为心肌梗死组、骨髓间充质干细胞移植组、血管内皮生长因子组和骨髓间充质干细胞+血管内皮生长因子组。建立兔心肌梗死模型,在心肌梗死后2周取107个骨髓间充质干细胞移植至梗死区。移植后4周测定心功能,梗死区骨髓间充质干细胞进行鉴定及计数,进行Ⅷ因子免疫组织化学染色。结果血流动力学比较发现,骨髓间充质干细胞+血管内皮生长因子组各项参数明显优于骨髓间充质干细胞组;心肌梗死区BrdU阳性细胞数骨髓间充质干细胞+血管内皮生长因子组明显多于骨髓间充质干细胞组(61.24±8.51个/视野比44.21±7.68个/视野,P<0.01);梗死区血管的数量骨髓间充质干细胞+血管内皮生长因子组(48.75±7.96个/视野)明显多于骨髓间充质干细胞组(33.08±6.12个/视野,P<0.01)、血管内皮生长因子组(29.98±8.04个/视野,P<0.01)和心肌梗死组(18.32±3.88个/视野,P<0.01)。结论转染血管内皮生长因子基因的骨髓间充质干细胞移植可改善兔心肌梗死后的心功能,其疗效明显优于单纯骨髓间充质干细胞移植及血管内皮生长因子基因治疗,可能是通过增加骨髓间充质干细胞的存活及改善梗死区的血供而起作用的。Aim To treat myocardial infarction（MI） with bone marrow mesenehymal stem eell（MSC） transplantation combined with vascular endothelial growth faetor（VEGF） gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group （ n = 12）, MS（2 group （ n = 12）, VEGF group （ n = 12）, MSC ＋ VEGF group （ M ＋ V group, n = 12）. Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery. 107 MSC were injected into the infarct-zone in four sites 2 weeks later in MSC and M ＋ V group, phVEGF gene were injeeted in infarct-zone in VEGF group and MSC transfeeted with phVEGF gene were injected in M ＋ V group. Heart function ineluding LVEDP, LVSP, LVDP, - dp/dtmax, ＋ dp/dtmax, were measured in vivo. The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain, immunohistochemieal stain of BrdU and Ⅷ factor antigen. Results The left ventrieular hemodynamies parameters showed that heart function were improved more in M ＋ V group than MSC group, MI group and VEGF group. The numbers of BrdU posivfive cell in M ＋ V group（ 61.24 ± 8.51 ）were more than in MSC group （44.21 ± 7.68, P 〈 0.01 ）. The numbers of vessels in infarcted zone were more in M ＋ V group （ 48.75 ± 7.96） than in MSC group （ 33.08 ± 6.12, P〈0.01）, VEGFgroup（29.98±8.04, P〈0.01）andM/group（18.32±3.88,P〈0.01）. Conclusions VEGF gene transfeeted MSC transplantation could improve heart function after myocardial infarction, and they were more effective than sole MSC transplantation. Keeping mere MSC survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.

关 键 词：内科学 心肌梗死 骨髓间充质干细胞 血管内皮生长因子 心功能 基因治疗 兔 

分 类 号：R542[医药卫生—心血管疾病]