探讨不同超声治疗时间对超声激励微泡空化增强小鼠MC38肿瘤血流灌注的影响，并对机制进行初步分析。

选取54只大腿内侧皮下种植MC38的荷瘤小鼠，利用飞依诺超声诊疗一体机Vflash模式激励微泡空化行超声治疗（MI=0.3）。小鼠按超声治疗时间（t）随机分为6组（n=9）：A组，t=1 min；B组，t=3 min；C组，t=5 min；D组，t=7 min；E组，t=10 min；F组（对照组），不接受超声治疗。每组治疗前后分别行超声造影检查，通过治疗前后峰值强度（PI）比、曲线下面积（AUC）比及肿瘤血流灌注面积比综合评估肿瘤血流灌注情况。治疗后，每组随机取2只小鼠肿瘤组织进行HE染色，观察治疗后病理学改变；取各组余下的7只小鼠肿瘤组织进行一氧化氮含量测定。

超声激励微泡空化治疗后，C、D、E组治疗前后PI比、AUC比及灌注面积比均明显高于对照组（P均<0.05）；其中D组治疗前后PI比、AUC比最高，明显高于C组（P<0.05）、B组（P<0.05）、A组（P<0.01），灌注面积比高于A组（P<0.01）、B组（P<0.05）。病理结果显示C、D、E组肿瘤微血管扩张充血，其中D组扩张微血管数量最多，充血最明显。超声治疗的各组肿瘤组织内一氧化氮含量较对照组增加，其中D组一氧化氮含量最高，但各组间差异无统计学意义（P>0.05）。

超声激励微泡空化可以增强小鼠MC38肿瘤血流灌注，超声治疗时间延长到5 min以上，肿瘤血流增强效果更加明显；超声治疗7 min时，超声肿瘤血流效应最为明显。其机制可能与超声激励微泡空化导致微血管扩张有关。

To investigate the effect of treatment with ultrasound-stimulated microbubbles (USMB) for different durations in enhancing blood perfusion in MC38 tumors in mice, and to analyze the underlying mechanism preliminarily.

A total of 54 tumor-bearing mice with MC38 tumor cells implanted subcutaneously on the inner thigh were selected and treated by microbubble cavitation stimulated using the VINNO US system in Vflash mode (mechanical index=0.3). The mice were randomly divided into 6 groups according to the treatment duration, with 9 mice in each group: Group A, t=1 min; Group B, t=3 min; Group C, t=5 min; Group D, t=7 min; Group E, t=10 min; Group F (control group), no ultrasound therapy. Contrast-enhanced ultrasound examinations were performed before and after treatment for each group, and tumor perfusion was evaluated comprehensively by peak intensity (PI) ratio, area under curve (AUC) ratio, and tumor perfusion area ratio before and after treatment.Two mice in each group were randomly selected to take tumor tissues for HE staining to observe the pathological changes after treatment. The remaining 7 mice in each group were collected for the determination of nitric oxide (NO) content.

After ultrasonic stimulation, the PI ratio, AUC ratio, and perfusion area ratio in Groups C, D, and E were significantly higher than those of the control group (P<0.05). Group D had the highest PI ratio and AUC ratio, which were significantly higher than those of Groups C (P<0.05), B (P<0.05), and A (P<0.01), and the perfusion area ratio in Group D was higher than those of Groups A (P<0.01) and B (P<0.05). The pathological results showed that the tumor microvessels in Groups C, D, and E were dilated and congested, with the number of dilated microvessels being most and congestion being most obvious in group D. The content of NO in tumor tissues of each group undergoing ultrasound therapy was higher than that of the control group. The content of NO in group D was the highest, but there was no significant difference among the groups (P>0.05).

Ultrasound-stimulated microbubbles can enhance blood perfusion of MC38 tumors in mice, and the enhancement effect is more obvious when the ultrasound treatment time is extended to more than 5 minutes. The best enhancement effect of tumor blood flow can be achieved when the ultrasound treatment time is 7 minutes. The therapeutic mechanism may be related to microvascular dilatation caused by ultrasound-stimulated microbubbles.