摘要
背景:超声辐射微泡已被大量应用于临床心肌微循环诊断,其安全性已得到证实。研究显示超声靶向破坏微泡可以使骨骼肌毛细血管破坏和局部红细胞渗出,可以促进细胞穿过内皮生理屏障。目的:探讨超声辐射微泡是否可以增加骨髓间充质干细胞移植治疗心肌梗死的效果。设计、时间及地点:随机对照动物观察,于2006-10/2008-05在东南大学医学院完成。材料:2月龄中国家猪20只,随机分为超声微泡组12只,细胞对照组8只。超声微泡对比剂SonoVue,国药准字J20030117,为上海博莱信谊药业有限责任公司产品。方法:无菌条件下抽取猪骨髓液,密度梯度离心法分离纯化骨髓间充质干细胞。两组动物均建立急性心肌梗死模型,造模后14d,超声微泡组通过OTW球囊导管先把2.4mL超声微泡对比剂SonoVue经冠状动脉注入左前降支中段,同时在体表给予1MHz,2W/cm2超声辐射心肌梗死区,连续辐射90s后,再注入超顺磁性氧化铁标记的骨髓间充质干细胞5×106个;细胞对照组同法仅单纯输注骨髓间充质干细胞。主要观察指标:采用64层螺旋CT检查心功能变化,光镜观察心肌组织学检测结果,电镜观察血管内皮细胞超微结构。结果:与移植前1d比较,移植后6周两组左心室射血分数均明显增加,且超声微泡组增加幅度高于细胞对照组(P<0.01)。与细胞对照组比较,超声微泡组普鲁士蓝阳性细胞数明显增多(P<0.01),且多数分布于心肌梗死周边区,有2例标本可见普鲁士蓝阳性细胞分化为新生血管内皮细胞;梗死周边区毛细血管密度明显升高(P<0.05)。两组心肌血管内皮细胞超微结构无差异,但移植后0h超声微泡组可见血管内皮间隙增宽。结论:超声辐射微泡可促进梗死心肌内猪自体骨髓间充质干细胞的移植,促进心肌血管新生,从而改善因心肌梗死而受损的心功能。
BACKGROUND： Ultrasound-mediated microbubble has been widely used in clinical myocardial microcirculation diagnosis, and its safety has been verified. Ultrasound target microvesicle can destroy skeletal nuscle blood capillary and local erythrocytes, and promote cells crossing endothelial physiologic barrier.
OBJECTIVE： To study whether ultrasound-mediated microbubbie enhances bone marrow mesenchymal stem cell （BMSC） transplantation for myocardial infarction.
DESIGN, TIME AND SETTING： The randomized controlled animal study was performed at the Medical College, Southeast University from October 2006 to May 2008. MATERIALS： A total of 20 pigs aged 2 months, and randomly assigned into ultrasound microvesicle group （n=12） and cell control group （n=8）. Opaque medium SonoVue （J20030117） was purchased from Bolaixinyi, Shanghai.
METHODS： Bone marrow was sterilely isolated. BMSCs were isolated and purified by the density gradient centrifugation. In both groups, acute myocardial infarction models were established. After 14 days, 2.4 mL SonoVue was infused into the left anterior descending branch of pigs in the ultrasound microvesicle group via the OTW Foley＇s tube through the coronary artery. Myocardial infarct region received 1 MHz, 2 W/cm2 ultrasonic radiation for 90 seconds. Subsequently, superparamagnetic iron oxide-labeled BMSCs （5x10B） were injected into pigs. In the cell control group, pigs only were subjected to BMSCs.
MAIN OUTCOME MEASURES： Heart function of pigs was checked by 64-spiral CT. Myocardial tissue was observed under an optical microscope. Ultrastructure of vascular endothelial cells was observed under the electron microscope. RESULTS： Compared with that 1 day pretransplantation, ejection fraction of the left ventricle significantly increased at 6 weeks following transplantation, and the increase was higher in the ultrasound microvesicte group than in the cell control group （P 〈 0.01 ）. Compared with the cell control group, number of Prussian blue-positive
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第23期4421-4425,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
