骨髓间充质干细胞膜微粒促进大鼠心肌梗死后血管新生  

Microparticles derived from bone marrow mesenchymal stem cells promote angiogenesis in rat myocardial infarction model

作　　者：耿志敏[1] 王珏[1] 范鸿洋 郑哲[2] 翁家侃[1] 孙成超[1] 褚茂平[1] 

机构地区：[1]温州医科大学附属第一医院,浙江温州325000 [2]中国医学科学院阜外心血管病医院,北京100037

出　　处：《中国病理生理杂志》2015年第8期1371-1375,共5页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金资助项目(No.LY14H020008);温州市科学技术局基金资助项目(No.Y20130169)

摘　　要：目的：观察骨髓间充质干细胞膜微粒（MSC-MPs）对大鼠心肌梗死后血管新生以及心功能的影响。方法：提取Sprague-Dawley大鼠MSCs并培养，在低氧低营养条件下培养72h，以诱导细胞凋亡释放MSC-MPs。将培养上清液超速离心获取MSC-MPs，透射电镜下观察其大小及形态，并用流式细胞术分析其表型。建立sD大鼠心肌梗死模型，心肌梗死边缘区注射膜微粒及对照试剂。超声心动图检测心功能，Masson染色检测心梗面积，免疫组织化学染色技术检测梗死边缘区血管a-平滑肌肌动蛋白和yonWillebrand因子以确定血管新生情况，real-timePCR检测心梗组织中血管内皮生长因子（VEGF）表达变化。结果：MSCs凋亡后可以释放膜微粒，MSC-MPs来自MSCs，直径为100-1000nm。心肌梗死大鼠心肌内注射MSC-MPs后，第7天和第28天时心功能明显改善，第28d时心梗面积比对照组减小，新生血管密度明显增加，第7天时心梗组织VEGF的表达增加。结论：MSC-MPs可以促进大鼠心肌梗死后的血管新生，改善心功能。AIM： To observe the effects of microparticles derived from bone marrow mesenchymal stem cells（ MSC-MPs） on angiogenesis and cardiac function in a rat myocardial infarction model. METHODS： MSCs were obtained from Sprague-Dawley rats. MSCs were treated under serum-free condition in hypoxia for 72 h,and the microparticles were isolated from the supernatants. The phenotypic profile of MSC-MPs was determined by bead-based flow cytometry and the morphology was observed under a transmission electron microscope. The rat myocardial infarction model was established.The cardiac function was evaluated by echocardiography after the intramyocardial injection of MSC-MPs. The myocardial infarct size was observed by Masson staining. The blood vessel density in the peri-infarcted area was measured using immunohistochemical staining for von Willebrand factor and α-smooth muscle actin. The expression of vascular endothelial growth factor（ VEGF） was analyzed by real-time PCR. RESULTS： Apoptotic MSCs released a large quantity of microparticles which were phenotypically similar to the parent MSCs and 100 - 1 000 nm in diameter. The cardiac functions of myocardial infarction rat model were improved at 7 d and 28 d after intramyocardial injection of MSC-MPs compared with control group.The myocardial infarct size was reduced and angiogenesis was promoted significantly in the infarcted heart injected with MSC-MPs 28 d after treatment. MSC-MPs treatment also increased the expression level of VEGF within 7 d. CONCLUSION： MSC-MPs protect cardiac tissue from ischemic injury and improve cardiac function by promoting angiogenesis after myocardial infarction.

关 键 词：骨髓间充质干细胞 微粒 心肌梗死 血管新生 

分 类 号：R363.2[医药卫生—病理学]