高强度聚焦超声非热效应对兔肝VX2肿瘤超微结构及细胞凋亡的影响

目的：观察高强度聚焦超声(high-intensity focused ultrasound，HIFU)热效应和非热效应损伤后兔肝VX2肿瘤的微观形态学变化。方法：将40只兔肝VX2肿瘤模型大白兔随机分为热效应组(n=20)和非热效应组(n=20)，每组于治疗后即刻及3，7，14 d分别随机处死5只，分析超微结构、凋亡相关蛋白表达及细胞凋亡情况。结果：电镜显示HIFU辐照后各时间点非热效应组的组织细胞破坏程度较热效应组严重。消融后两组交界区凋亡相关蛋白即刻及3 d血管内皮生长因子(vascular endothelial growth factor，VEGF)呈低水平表达，7~14 d均逐渐升高，各时间点两组相比差异均无统计学意义(均P>0.05)；caspase-3治疗后3 d表达达到高峰，3与7 d时非热效应组表达明显高于热效应组(均P<0.05)；NF-κB的表达3 d时开始增加，7 d达高峰，14 d开始下降，各时间点两组相比差异无统计学意义(均P>0.05)。TUNEL检测HIFU治疗后交界区凋亡阳性细胞，发现3与7 d非热效应组高于热效应组(均P<0.01)，凋亡指数分别为(28.60±1.14)%，(21.80±1.92)%和(21.00±1.58)%，(14.80±1.48)%。结论：HIFU热效应及非热效应机制均能诱导交界区凋亡产生，而后者效果更为强烈。

Non-thermal effect of high-intensity focused ultrasound on ultrastructure and apoptosis in rabbit hepatic VX2 tumors

Objective: To observe the micromorphological changes of ultrastructure, apoptosis-related proteins expression and tumor cell apoptosis after ablation with the high-intensity focused ultrasound (HIFU), and to explore the mechanisms responsible for the thermal and non-thermal eff ect.Methods: Forty rabbits with hepatic VX2 tumors were randomly divided into a thermal group(n=20) and a non-thermal group (n=20), and were subjected to HIFU ablation with thermal ornon-thermal condition, respectively. Five animals in each group were sacrificed on the 1st, 3rd, 7thor 14th day after the ablation. The changes of ultrastructure, apoptosis-related proteins expressionand tumor cell apoptosis were detected.Results: The results of transmission electron microscope (TEM) revealed more severe injury ontissue and cells in the non-thermal group than that in the thermal group. The changes of apoptosisrelatedproteins expression and tumor cell apoptosis in transient zone were significantly different incomparison with that in the ablated area or peripheral area between the two groups. The expressionof vascular endothelial growth factor (VEGF) was at low level on the 1st and 3rd day and elevatedgradually on the 7th and 14th day, with no significant difference (all P>0.05). The expression ofcaspase-3 reached peak on the 3rd day and decreased on the 7th and 14th day. It was significantlyhigher in the non-thermal group than that in the thermal group on the 3rd and 7th day (all P<0.05).The expression of NF-κB was elevated from the 3rd day and reached peak on the 7th day whiledecreased on the 14th day. There was no significant difference at every time point between the 2groups (all P>0.05). The apoptosis index in the non-thermal group and the thermal group on the3rd and 7th day were (28.60±1.14)% vs (21.80±1.92)% and (21.00±1.58)% vs (14.80±1.48)%,respectively. It was higher in the non-thermal group than that in the thermal group (both P<0.01).Conclusion: Both the thermal and the non-thermal effect of HIFU can induce apoptosis intransient zone, but the latter have a stronger effect.