超声微泡造影剂对大鼠骨骼肌毛细血管通透性的影响

Ultrasound-mediated microbubble destruction increases capillary permeability in rat skeletal muscles

目的研究治疗剂量超声破坏微泡造影剂对大鼠骨骼肌毛细血管通透性的影响。方法以伊文思蓝(EB)为指示剂,18只清洁级SD大鼠,随机均分为EB组(E)、EB+超声组(E+U)和EB+超声+微泡组(E+U+M)共3组进行实验。给予相同参数条件的超声进行照射,经颈动脉输/不输入微泡造影剂,在体荧光显微镜下观察EB外溢情况并行视觉评分;使用标准曲线和分光光度法测量各组大鼠脊斜肌中EB的含量。结果E+U+M组镜下可见微血管周围EB外溢,视觉评分等级为2级,显著高于E组(0级)及E+U组(0-1级)(P<0.05)。E组及E+U组两者相比无显著性差异(P>0.05)。E+U+M组脊斜肌中EB含量为(51.57±3.89)μg/g,比E组[(28.99±4.67)vg/g]及E+U组[(30.99±4.11)μg/g]明显增加(P<0.05)。E组及E+U组两者相比无显著性差异(P>0.05)。结论超声介导微泡造影剂破坏可使脊斜肌组织毛细血管通透性增加,可能是超声微泡造影剂增强基因转染的主要机制之一。

Objective To investigate the effects of ultrasound mediated microbubble destruction on capillary permeability in rat skeletal muscles. Methods Eighteen SD rats were randomized into 3 groups, namely the Evans blue （EB） group, EB＋ultrasound （E＋U） group and EB＋microbubble＋ultrasound （U＋E＋M） group with corresponding treatments, using EB injected into the carotid artery as the indicator for capillary permeability, The microbubbles were injected through the carotid artery with fixed ultrasound parameters. The spillover of EB was estimated under fluorescence microscope according to the visual staining scores. The contents of EB in the skeletal muscles were calculated according to the standard curve and spectrophotometry. Results EB spiUover was observed around the capillaries in E＋U＋M group, which had a significantly higher visual score than EB group and E＋U group （0 and 0-1, respectively, P〈0.05）. The EB content was 51.57±3.89 μg/g in E＋U＋M group, also significantly higher than those in EB group （28.99±4.67μg/g） and E＋U group （30.99±4.11 μg/g） （P〈0.05）. Conclusion Exposure to both ultrasound and microbubble contrast agents results in increased capillary permeability of rat skeletal muscles, which might be an important mechanisms for gene delivery enhancement by ultrasound contrast agents.