Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals
Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals
复制标题
超声靶向微泡破坏可增强 BMC 的延迟输送，并通过诱导植入信号减弱梗塞后心脏重塑。
DOI：
10.1042/cs20160085
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发表时间：
2016-12-01
期刊：
影响因子：
6
通讯作者：
Bin, Jianping
中科院分区：
文献类型：
--
作者：
Chen, Yanmei;Zhang, Chuanxi;Bin, Jianping
在急性心肌梗死（MI）患者成功再灌注后2-4周延迟给予骨髓细胞（BMC）并不能改善心功能。在此时间间隔后观察到的植入信号减少可能会损害延迟BMC治疗的效果。在本研究中，我们的目的是确定超声靶向微泡破坏（UTMD）治疗是否可以增加植入信号，增强延迟BMC的输送，并随后减弱梗死后心脏重塑。结扎Wistar大鼠左冠状动脉45 min后再灌注，建立心肌缺血/再灌注（I/R）模型。Western印迹显示植入信号在I/R后7天达到峰值，在I/R后14天显著降低。在I/R后14天较低的植入信号可以由UTMD处理在1.0-1.9的机械指数触发。机械指数1.9组的肌钙蛋白I水平高于其他组。苏木精-伊红染色和荧光染色显示，UTMD和延迟移植组移植的骨髓细胞数量明显多于对照组（P<0.05）。UTMD组和延迟移植BMC组治疗后4周心功能改善，心肌纤维化程度减轻，与对照组比较差异均有统计学意义（P <0.05）。组织学检查显示UTMD联合延迟移植的BMC可增加毛细血管密度、心肌细胞增殖和c-kit+细胞增殖。这些结果表明，UTMD治疗可以诱导植入信号，并增强延迟的BMCs归巢到缺血心肌，通过促进新血管形成、心肌形成和心脏c-kit+细胞扩增来减弱梗死后心脏重塑。
Delayed administration of bone marrow cells (BMCs) at 2–4 weeks after successful reperfusion in patients with acute myocardial infarction (MI) does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. In the present study, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0–1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous haematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischaemic zone was greater in the group treated with both UTMD and delayed BMC transplantation than in the control groups (P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (bothP<0.05). Histopathology demonstrated that UTMD combined with delayed BMC transplantation increased capillary density, myocardial cell proliferation and c-kit+cell proliferation. These findings indicated that UTMD treatment could induce engraftment signals and enhance homing of delayed BMCs to ischaemic myocardium, attenuating post-infarction cardiac remodelling by promoting neovascularization, cardiomyogenesis and expansion of cardiac c-kit+cells.