目的探讨低频超声辐照微泡(USMB)阻断裸鼠人前列腺癌PC3皮下移植瘤血流的时间及观察血流恢复的过程。方法采用USMB治疗裸鼠皮下PC3移植瘤,比较治疗前及治疗后各时间点移植瘤的造影平均峰值强度(API)、达峰时间(TP)及组织学改变。结果治疗后即刻,移植瘤的API从68.63±5.25降至18.01±2.73,与治疗前相比差异有统计学意义(P〈0.001);TP从(32.28±6.18)s增至(72.63±7.47)S,与治疗前相比差异有统计学意义(P〈0.001);治疗后3h,血流灌注逐渐恢复;治疗后4h,恢复至治疗前水平。组织学检查显示,治疗后即刻移植瘤微血管扩张、破裂和血管内外血栓形成;治疗后30min、1h和2h,血管外血肿和血栓逐渐消失;治疗后3h,血管内血栓显著缩小;治疗后4h后,血管内血栓进一步逐渐缩小,血管扩张程度逐渐减轻;治疗后12h,瘤组织基本恢复至治疗前。结论USMB阻断裸鼠PC3皮下移植瘤血供的最佳时间是治疗后2h内,血流再通可能主要由于肿瘤微血管内血栓溶解所致。
Objective To explore the duration of blood blocking effect and recovery process induced by low-frequency ultrasound combining microbubbles (USMB) on prostate cancer xenografts. Methods A total of 88 nude mice undergoing USMB was studied. Contrast enhanced ultrasound, Hemotoxylin and eosin staining, and modified Martius-Sarlet-Blue staining were used to compared the average peak intensity(API), time to peak intensity(TP) and histological alteration before and after treatment. Results Immediately after the treatment, the tumor contrast perfusion completely disappeared, API dropped from 68.63 ± 5.25 to 18.01± 2.73 ( P 〈0.001,vs pre-treatment) and TP increased from (32.28 ± 6.18)s to (72.63 ± 7.47)s (P〈0.001,vs pre-treatment). At 30 minutes and 1 hour after treatment, the tumor perfusion remained defect. At 2 hours after treatment, rarely dotted enhancement was showed. The differences among the three groups in API and TP at 30 minutes, 1 hour and 2 hours after treatment were not significant (all P〉0.05). From post-3 hours after treatment ,the tumor perfusion began a process of perfusion recovery, and showed nodular or large patch of heterogeneous enhancement. API at 3 hours after treatment was 51.99 ±6.20 (P〈0. 001, vs post treatment immediately), and TP decreased to (50.41 ±6.51 )s ( P 〈0. 001, vs post treatment immediately). At 4 hours, 5 hours, 6 hours, 12 hours and 24 hours after treatment , CEUS showed homogeneous and rich enhancement,and there was no significant difference in both API and TP, compared with those pre-treatment (all P 〉 0.05, vs pre-treatment). Histological examinations showed that, immediately after treatment, microvessels severely dilated, ruptured and intravascular and extravascular thrombi formed. At 30 minutes, 1-hour and 2-hour after treatment,extravascular thrombi and hematomas gradually disappeared. From 3-hour after treatment, vessel dilation was lessened,and intravascular thrombi gradually shrank. At 12-hour after treatme