自体骨髓间充质干细胞移植急性心肌梗死犬血管内皮生长因子及血管新生的变化

Changes in vascular endothelial growth factor and angiogenesis in dogs with acute myocardial infarction following autologous bone marrow mesenchymal stem cells transplantation

背景:研究表明骨髓间充质干细胞在体内外可诱导分化为心肌样细胞,局部移植骨髓间充质干细胞可以促进血管新生,阻止心室重构,改善心功能,但具体机制尚未阐明。目的:探讨骨髓间充质干细胞心肌移植后犬体内血管内皮生长因子的表达变化以及对心肌梗死区血管新生的影响。方法:健康杂种犬随机分成实验组和对照组,均建立急性心肌梗死模型。建模后一二小时,实验组犬将BrdU标记的骨髓间充质干细胞悬液注入心肌梗死区四五个不同部位,对照组注入等量的DMEM。骨髓间充质干细胞移植4周后,酶联免疫吸附测定法检测血清中的血管内皮生长因子浓度,并采用免疫组化染色法进行毛细血管密度测定。结果与结论:移植后第1天及1,2,3,4周血管内皮生长因子的浓度实验组与对照组相比均增加(P<0.01),且两组血管内皮生长因子的浓度均随时间呈下降趋势(P<0.01);心肌梗死区单位面积毛细血管数实验组较对照组明显增加(P<0.01)。结果表明心肌梗死区移植骨髓间充质干细胞后使得体内血管内皮生长因子的浓度增加,并可促进心肌梗死后毛细血管新生。

BACKGROUND：Bone marrow mesenchymal stem cells（BMSCs） can be induced to differentiate into cardiomyocyte-like cells in vivo and in vitro.BMSCs transplantation in local region can promote angiogenesis,prevent ventricle reconstruction,and improve cardiac function,but precise mechanisms remain unclear.OBJECTIVE：To investigate vascular endothelial growth factor（VEGF） expression and angiogenesis in myocardial infarction zone following BMSCs cardiac transplantation in dogs.METHODS：Healthy hybrid dogs were randomly assigned to experimental and control groups.All dogs were used to establish models of acute myocardial infarction.At 1 and 2 hours following model induction,BrdU-labeled BMSC suspension was infused into four or five regions of myocardial infarction region in the experimental group,whereas an equal volume of Dulbecco＇s modified Eagle＇s medium was injected into the dogs of control group.At 4 weeks following transplantation,VEGF concentration in serum was determined using enzyme-linked immunosorbent assay（ELISA）.Capillary density was detected using immunohistochemical staining.RESULTS AND CONCLUSION：On day 1,weeks 1,2,3 and 4 following transplantation,VEGF concentrations were increased in the experimental group compared with control group（P 〈0.01）.Moreover,VEGF concentrations were decreased over time in two groups（P 〈0.01）.Capillaries per unit area of the experimental group were significantly increased in infarct region compared with control group（P〈 0.01）.Results showed that after BMSCs transplantation,in myocardial infarct area,the concentration of VEGF is increased and promotes angiogenesis after myocardial infarction.