超声靶向破碎微泡对心肌梗死犬心肌微环境的影响

The Changes of Myocardial Microenvironment Induced by Ultrasound-Targeted Microbubble Destruction in a Canine Myocardial Infarction Model

为了研究超声靶向破碎微泡对犬心肌梗死模型局部心肌微环境的影响。将10只犬随机分为实验组与对照组,每组5只犬,结扎犬左前降支,建立心肌梗死模型。建立心肌梗死模型后1周,将实验组每只模型犬用脉冲超声(强度为1.0 W/cm2,频率为1 MHz)经胸辐照心肌,辐照时间共为10 min,同时静脉注入2 m L超声微泡。按照上述方法,每隔2 d处理一次,一共处理3次。对照组中的模型犬不经预处理。在所有犬心肌梗死模型建立后两周左右处死所有实验犬,取出心脏,于心肌梗死周边区域选取相应心肌组织,并送检。所取组织均采用免疫组织化学染色法、Western blotting法及定量实时PCR法分别从蛋白以及基因水平测量局部心肌组织内VCAM-1、VEGF、SDF-1和IL-1β的含量,从而探讨超声靶向辐照破碎微泡对犬心肌梗死模型局部心肌微环境的影响。免疫组织化学染色法及Western blotting法从蛋白水平定性和半定量观察到实验组中梗死周边区心肌分泌的VCAM-1、VEGF、SDF-1和IL-1β量明显多于对照组心肌梗死周边区;定量实时PCR法从基因水平定量分析检测显示实验组内梗死周边区心肌分泌VCAM-1、VEGF、SDF-1和IL-1β明显高于对照组中心肌梗死周边区(p<0.05)。采用一定量的超声被动靶向辐照破碎微泡能够引发心肌内源性生物活性物质的分泌,促进VCAM-1、VEGF、SDF-1和IL-1β的高表达,从而使局部心肌微环境得到一定改变,有利于干细胞移植治疗缺血性心脏病。

In order to investigate the changes of myocardial microenvironment after MI induced by ultrasound-targeted microbubble destruction. Ten dogs were randomly divided into treatment group and control group after the establishment models of myocardial infarction. One week later, dogs in the treatment group were treated with an ultrasound at a frequency of I MHz and an intensity of 1.0 W/cm2 media microbubble destruction for three times in one week; There was no treatment for dogs in the control group. Levels of vascular endothelial growth factor （VEGF）, stromal cell-derived factor- 1 （SDF- 1）, vascular cell adhesion molecule- 1 （VCAM- 1） and interleukin- 1β （IL-1β） in the myocardium were measured by real-time RT-PCR and western blot analyses in half of the dogs in each group after 2 weeks. Ultrasound at a frequency of 1 MHz and an intensity of 1.0 W/cm2 provoked in-flammatory reactions with mild myocardial damage. The expression ofVEGF, SDF-1, VCAM-1 and IL-1β in the treatment group was much higher than the control group. The expression of VEGF, SDF-1, VCAM-1 and IL-1β caused by UTMD may change the focal myocardial microenvironment.