超声介导的微泡破坏增强了骨髓干细胞冠状动脉内移植对心肌梗死的治疗效果。
Ultrasound-mediated microbubble destruction enhances the therapeutic effect of intracoronary transplantation of bone marrow stem cells on myocardial infarction.
作者信息
Chang Xuefeng, Liu Jiaqing, Liao Xudong, Liu Guohui
机构信息
Department of Emergency Surgery, First Hospital of Jilin University Changchun 130021, Jilin, China.
Department of Radiation Medicine, School of Public Health of Jilin University Changchun 130021, Jilin, China.
出版信息
Int J Clin Exp Pathol. 2015 Feb 1;8(2):2221-34. eCollection 2015.
OBJECTIVE
The combination of intracoronary transplantation and ultrasound-mediated microbubble destruction may promote effective and accurate delivery of bone marrow stem cells (BMSCs) into the infarct zone. To test this hypothesis in this study we examined the effectiveness of ultrasound-mediated microbubble destruction in combination with intracoronary transplantation of BMSCs for the treatment of myocardial infarction in canine model of acute myocardial infarction.
METHOD
The dogs were randomly assigned to four groups: PBS, ultrasound-mediated microbubble destruction, BMSCs, BMSCs together with ultrasound-mediated microbubble destruction. At 28 days post-surgery, cardiac function and the percentage of perfusion defect area to total left ventricular perfusion area (DA%) were determined by myocardial contrast echocardiography. Nitro blue tetrazolium staining was performed to determine myocardial infarct size, hematoxylin and eosin staining for assessing microvascular injury, Masson's staining for analyzing myocardial tissue collagen, immunohistochemical analysis of α-actin to measure cardiac contractile function and of BrdU-labeled myocardial cells to measure the number of the BMSCs homing to the infarcted region.
RESULTS
The transplantation of BMSCs significantly improved heart function and DA% (P < 0.05). The group that received ultrasound-mediated microbubble destruction with BMSCs transplantation showed the most improvement in heart function and DA% (P < 0.05). This group also showed a denser deposition of BMSCs in the coronary artery and more BrdU positive cells in the infarcted region, had the maximum number of α-actin positive cells, showed the smallest myocardial infarct area compared to other groups (P< 0.05).
CONCLUSION
Ultrasound-mediated microbubble destruction increases the homing of BMSCs in the target area following intracoronary transplantation, which allows more BMSCs to differentiate into functional cardiomyocytes, thereby reducing myocardial infarct size and improving cardiac function.
目的
冠状动脉内移植联合超声介导的微泡破坏可能促进骨髓干细胞（BMSCs）有效且准确地输送至梗死区域。为在本研究中验证这一假设，我们检测了超声介导的微泡破坏联合冠状动脉内移植BMSCs对急性心肌梗死犬模型心肌梗死的治疗效果。
方法
将犬随机分为四组：磷酸盐缓冲液（PBS）组、超声介导的微泡破坏组、BMSCs组、BMSCs联合超声介导的微泡破坏组。术后28天，采用心肌对比超声心动图测定心功能及灌注缺损面积占左心室总灌注面积的百分比（DA%）。进行硝基蓝四氮唑染色以测定心肌梗死面积，苏木精-伊红染色评估微血管损伤，Masson染色分析心肌组织胶原，免疫组化分析α-肌动蛋白以测量心脏收缩功能，分析BrdU标记的心肌细胞以测量归巢至梗死区域的BMSCs数量。
结果
BMSCs移植显著改善了心功能和DA%（P<0.05）。接受超声介导的微泡破坏联合BMSCs移植的组在心功能和DA%方面改善最为明显（P<0.05）。该组还显示冠状动脉中BMSCs沉积更密集，梗死区域BrdU阳性细胞更多，α-肌动蛋白阳性细胞数量最多，与其他组相比心肌梗死面积最小（P<0.05）。
结论
超声介导的微泡破坏增加了冠状动脉内移植后BMSCs在靶区域的归巢，使更多BMSCs分化为功能性心肌细胞，从而减小心肌梗死面积并改善心功能。
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