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目的探讨高强度聚焦超声(HIFU)治疗小鼠前列腺癌引起的肿瘤凝固性坏死区中存在的肿瘤亚致死损伤,以及HIFU联合放疗对其的影响。方法建立小鼠前列腺癌皮下移植瘤模型,设对照组、HIFU组、低剂量放疗组、放疗组和HIFU联合低剂量放疗组,各组测定肿瘤坏死面积百分比(NAP),并通过TUNEL法和抗CD34微血管染色分别检测残留存活肿瘤组织的凋亡细胞密度(AD)和微血管密度(MVD)。结果与对照组比较,HIFU组NAP(41.18±6.44)%显著增加,肿瘤凝固性坏死区的周边虽残留存活肿瘤组织,但存活肿瘤组织的AD(61.78±20.95)个/视野显著增加,MVD显著降低(P<0.05)。放疗组和低剂量放疗组各项指标差异无统计学意义(P<0.05)。HIFU联合低剂量放疗组与HIFU组和2个放疗组比较,NAP(77.95±6.19)%显著增加,残留存活肿瘤组织的AD(183.33±33.62)个/视野显著增加(P<0.05)。析因方差分析示HIFU和放疗间存在显著的协同增效效应(P<0.01)。结论HIFU治疗小鼠前列腺癌时,凝固性坏死区周边残留的存活肿瘤组织存在亚致死损伤。HIFU联合低剂量放疗存在协同增效效应,能减少肿瘤的亚致死性损伤,促进肿瘤组织凝固性坏死和肿瘤细胞凋亡,疗效优于单独的放疗或HIFU治疗。
Objective To investigate the sublethal damage induced by high intensity focused ultrasound (HIFU) in the area of tumor coagulation necrosis caused by prostate cancer in mice and the effect of HIFU combined with radiotherapy on it. Methods A subcutaneous xenograft model of mouse prostate cancer was established. The control group, HIFU group, low-dose radiotherapy group, radiotherapy group and HIFU combined with low-dose radiotherapy group were established. Tumor necrosis area percentage (NAP) CD34 microvessel staining was used to detect apoptotic cell density (AD) and microvessel density (MVD) in surviving tumor tissue. Results Compared with the control group, NAP (41.18 ± 6.44)% in HIFU group was significantly increased. Surviving remaining tumor tissue around the tumor coagulation necrosis area, however, AD (61.78 ± 20.95) / visual field of surviving tumor tissue was significantly increased and MVD was significant Decreased (P <0.05). Radiotherapy group and low-dose radiotherapy group, there was no significant difference between the various indicators (P <0.05). Compared with HIFU group and two radiotherapy groups, NAP (77.95 ± 6.19)% increased significantly in HIFU combined with low dose radiotherapy group, AD (183.33 ± 33.62) / visual field in residual survived tumor tissue increased significantly (P <0.05). Factor analysis of variance showed a significant synergistic effect between HIFU and radiotherapy (P <0.01). Conclusion When HIFU is used to treat mouse prostate cancer, there is sublethal damage in the surviving tumor tissue around the coagulation necrosis area. HIFU combined with low-dose radiotherapy synergistic effect exists, can reduce the sublethal tumor damage, promote tumor tissue coagulation necrosis and tumor cell apoptosis, the effect is superior to radiotherapy alone or HIFU treatment.