超声辐照联合静脉输注微泡对大鼠急性心肌梗死微循环的改善作用
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摘要
目的观察超声辐照联合静脉输注微泡对大鼠急性心肌梗死微循环的改善作用。方法将10周SD大鼠90只分为三组:超声微泡组、超声组及单纯心梗组,每组各30只。各组大鼠均成功制备心肌梗死模型后,超声微泡组大鼠经舌下静脉输注微泡并应用超声辐照心脏,超声组舌下输注生理盐水并联合超声辐照心脏,单纯心梗组心梗大鼠不做任何处理。记录大鼠心梗前及心梗后心电图的变化情况,心梗后第3天,电镜观察梗死区心肌变化。心梗后28 d,取大鼠心脏行HE染色计数梗死区血管密度。结果超声微泡组大鼠9只于心梗后出现室性心律失常,超声组只有1只大鼠出现室性心律失常,单纯心梗组无上述变化,超声微泡组与其余两组比较差异有统计学意义(P <0.05)。心梗后第3天,超声微泡组大鼠心肌微结构优于其他组。心梗后第28天,观察梗死区微血管密度显示,超声微泡组血管环数最多,高于超声组、单纯心梗组(P <0.05)。超声组与单纯心梗组血管环计数比较差异无统计学意义。结论超声辐照联合微泡可改善大鼠心肌梗死后梗死区心肌的微循环,这可能与超声微泡产生的物理效应引发梗死区心肌再灌注有关。
Objective To observe the effects of ultrasound irradiation combined with intravenous microbubbles on microcirculation in rats with acute myocardial infarction. Methods Ninety SD rats(10-week-old) were divided into three groups(30 rats in each group) :ultrasound combined with microbubble group,ultrasound group and simple myocardial infarction group. After successful preparation of myocardial infarction model,the rats in ultrasound combined with microbubble group were infused with microbubbles via sublingual vein and irradiated by ultrasound. The rats in ultrasound group were infused with normal saline and irradiated by ultrasound. The rats in simple myocardial infarction group were not given any treatment. The changes of electrocardiogram before and after myocardial infarction in rats were recorded. The changes of myocardium in infarcted area were observed under electron microscopy at 3 d after myocardial infarction. At 28 d after myocardial infarction,the rat hearts were taken for HE staining to count the vascular density in the infarcted area. Results The ventricular arrhythmia occurred in 9 rats in ultrasound combined with microbubble group after myocardial infarction,and only one rat in ultrasound group. No ventricular arrhythmia was found in simple myocardial infarction group. There was a significant difference in the incidence of ventricular arrhythmia between ultrasound combined with microbubbles group and the other two groups(P < 0.05). At 3 d after myocardial infarction,the ultrastructure of myocardial cells in ultrasound combined with microbubbles group was superior to that of the other groups under electron microscopy. At 28 d after myocardial infarction,the number of vascular rings in ultrasound combined with microbubbles group was higher than that in ultrasound group and simple myocardial infarction group according to the microvessel density of infarcted area(P < 0.05). There was no significant difference in ring counts between ultrasound group and simple myocardial infarction group. Conclusion Ultrasound combined with microbubbles can improve myocardial microcirculation in infarcted area of rats after myocardial infarction,which may be related to myocardial reperfusion induced by physical effects of ultrasound microbubbles.
Objective To observe the effects of ultrasound irradiation combined with intravenous microbubbles on microcirculation in rats with acute myocardial infarction. Methods Ninety SD rats(10-week-old) were divided into three groups(30 rats in each group) :ultrasound combined with microbubble group,ultrasound group and simple myocardial infarction group. After successful preparation of myocardial infarction model,the rats in ultrasound combined with microbubble group were infused with microbubbles via sublingual vein and irradiated by ultrasound. The rats in ultrasound group were infused with normal saline and irradiated by ultrasound. The rats in simple myocardial infarction group were not given any treatment. The changes of electrocardiogram before and after myocardial infarction in rats were recorded. The changes of myocardium in infarcted area were observed under electron microscopy at 3 d after myocardial infarction. At 28 d after myocardial infarction,the rat hearts were taken for HE staining to count the vascular density in the infarcted area. Results The ventricular arrhythmia occurred in 9 rats in ultrasound combined with microbubble group after myocardial infarction,and only one rat in ultrasound group. No ventricular arrhythmia was found in simple myocardial infarction group. There was a significant difference in the incidence of ventricular arrhythmia between ultrasound combined with microbubbles group and the other two groups(P < 0.05). At 3 d after myocardial infarction,the ultrastructure of myocardial cells in ultrasound combined with microbubbles group was superior to that of the other groups under electron microscopy. At 28 d after myocardial infarction,the number of vascular rings in ultrasound combined with microbubbles group was higher than that in ultrasound group and simple myocardial infarction group according to the microvessel density of infarcted area(P < 0.05). There was no significant difference in ring counts between ultrasound group and simple myocardial infarction group. Conclusion Ultrasound combined with microbubbles can improve myocardial microcirculation in infarcted area of rats after myocardial infarction,which may be related to myocardial reperfusion induced by physical effects of ultrasound microbubbles.
引文
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[7]冯骞,杨莉,邱世锋,等.三维超声联合静脉滴注微泡对急性心肌梗死猪冠状动脉及心肌微循环的影响[J].山东医药,2017,57(32):48-50.
[8]张静,马爱群,魏峰,等.大鼠骨髓间充质干细胞在心肌缺血微环境中Cav1.2的表达[J].山西医科大学学报,2017,48(11):1092-1095.
[9]Ren JL,Wang ZG,Zhang Y,et al.Transfection efficiency of TDL compound in HUVEC enhanced by ultrasound-targeted microbubble destruction[J].Ultrasound Med Biol,2008,34(11):1857-1867.
[10]D’Amario D,Leone AM,Galiuto L,et al.Diagnostic ultrasound impulses improve microvascular flow in patients with STEMI receiving intravenous microbubbles[J].J Am Coll Cardiol,2016,68(18):2030-2031.
[11]Yoshida J,Ohmori K,Takeuchi H,et al.Treatment of ischemic limbs based on local recruitment of vascular endothelial growth factor-producing inflammatory cells with ultrasonic microbubble destruction[J].J Am Coll Cardiol,2005,46(5):899-905.
[12]Song X,Zhu H,Jin L,et al.Ultrasound-mediated microbubble destruction enhances the efficacy of bone marrow mesenchymal stem cell transplantation and cardiac function[J].Clin Exp Pharmacol Physiol,2009,36(3):267-271.
[2]Xie F,Slikkerveer J,Gao S,et al.Coronary and microvascular thrombolysis with guided diagnostic ultrasound and microbubbles in acute ST segment elevation myocardial infarction[J].Am Soc Echocardiogr,2011,24(12):1400-1408.
[3]Li H,Lu Y,Sun Y,et al.Diagnostic ultrasound and microbubbles treatment improves outcomes of coronary no-reflow in canine models by sonothrombolysis[J].Crit Care Med,2018,46(9):e912-e920.
[4]任国瑞,滕金龙,康维强,等.冠状动脉粥样硬化性心脏病血管重构与斑块组成的血管内超声研究[J].中华超声影像学杂志,2015,24(2):105-108.
[5]胡波,姜楠,曹省,等.超声辐照十二氟戊烷相变纳米微泡治疗冠状动脉微循环血栓栓塞的体外实验研究[J].中华超声影像学杂志,2017,26(9):808-812.
[6]Goyal A,Yu FTH,Tenwalde MG,et al.Inertial cavitation ultrasound with microbubbles improves reperfusion efficacy when combined with tissue plasminogen activator in an in vitro model of microvascular obstruction[J].Ultrasound Med Biol,2017,43(7):1391-1400.
[7]冯骞,杨莉,邱世锋,等.三维超声联合静脉滴注微泡对急性心肌梗死猪冠状动脉及心肌微循环的影响[J].山东医药,2017,57(32):48-50.
[8]张静,马爱群,魏峰,等.大鼠骨髓间充质干细胞在心肌缺血微环境中Cav1.2的表达[J].山西医科大学学报,2017,48(11):1092-1095.
[9]Ren JL,Wang ZG,Zhang Y,et al.Transfection efficiency of TDL compound in HUVEC enhanced by ultrasound-targeted microbubble destruction[J].Ultrasound Med Biol,2008,34(11):1857-1867.
[10]D’Amario D,Leone AM,Galiuto L,et al.Diagnostic ultrasound impulses improve microvascular flow in patients with STEMI receiving intravenous microbubbles[J].J Am Coll Cardiol,2016,68(18):2030-2031.
[11]Yoshida J,Ohmori K,Takeuchi H,et al.Treatment of ischemic limbs based on local recruitment of vascular endothelial growth factor-producing inflammatory cells with ultrasonic microbubble destruction[J].J Am Coll Cardiol,2005,46(5):899-905.
[12]Song X,Zhu H,Jin L,et al.Ultrasound-mediated microbubble destruction enhances the efficacy of bone marrow mesenchymal stem cell transplantation and cardiac function[J].Clin Exp Pharmacol Physiol,2009,36(3):267-271.