摘要目的 观察预防性脑照射(PCI)对小鼠黑色素瘤脑转移灶生长和血管新生的影响并探讨其机制.方法 PCI组小鼠在颅内种植肿瘤1周前接受25 Gy的全脑照射,对照组小鼠接受伪照射.立体定向微量注射法建立C57/BL6小鼠同源性黑色素瘤B16F10Luc2颅内转移瘤.活体生物荧光发光技术定量测定颅内的肿瘤负荷,并进行生存分析.免疫荧光组织化学测定并比较两组肿瘤组织、对侧正常脑组织的CD31和CD105标记的微血管密度(MVD)和微血管面积(MVA).结果 肿瘤颅内种植后第10天PCI组颅内转移瘤活体荧光强度明显低于对照组(P＜0.05);生存分析显示PCI组动物中位数存活时间(1Sd)显著长于对照组(16 d)(P＜0.05);两组的肿瘤组织内的MVD[对照组(10.933±3.058)个/0.148mm2,PCI组(13.067±3.150)个/0.148mm2]均显著低于对侧脑组织[对照组(17.200±2.859)个/0.148 mm2,PCI组(16.267±2.434)个/0.148 mm2,P＜0.05],PCI组的CD105-MVD[(0.867 ±0.990)个/0.148 mm2]及CD31-MVA[(1.622 ±0.440)％]都显著低于对照组[CD105-MVD:(2.200±1.146)个/0.148 mm2,CD31-MVA:(2.219 ±0.712)％,P＜0.05].结论 PCI对小鼠黑色素瘤颅内转移灶生长和非出芽性血管新生有显著的抑制作用,其机制有待进一步研究.

abstractsObjective To study the impact of prophylactic cranial irradiation (PCI) on growth and angiogenesis of murine brain metastasis of syngeneic melanoma.Methods One week prior to implantation,eight mice from prophylactic cranial irradiation (PCI) group received PCI with total dosage of 25 Gy in 10 fractions,while eight mice from control group only received sham irradiation.The intracranial metastases of B16F10Luc2 melanoma syngeneic to C57/BL6 mice were established with stereotactic micro-injection implantation.In vivo bioluminescence,representing intracranial tumor burden,were quantitatively measured and survival analysis was carried out.Microvessel density (MVD) and microvessel area(MVA) labelled by anti-CD31 and anti-CD105 staining were analyzed.Results In vivo fluorescence intensity of PCI group was significant lower than control group (P ＜ 0.05) on the 10th day post-implantation.Survival analysis showed that the median survival time of PCI group (18 days) was longer than control group (16 days) (P ＜ 0.05).MVD within tumor tissue in both groups[(10.933 ± 3.058)/0.148 mm2] were significantly lower than the contralateral brain tissue [(17.200 ± 2.859)/0.148 mm2 for control group and (16.267 ± 2.434)/0.148 mm2 for PCI group,P ＜ 0.05].CD105-MVD [(0.867 ± 0.990)/0.148 mm2] and CD31-MVA[(1.622 ± 0.440)％] within tumor of PCI group were significantly lower than control group [CD105-MVD:(2.200 ± 1.146)/0.148 mm2,CD31-MVA:(2.219 ± 0.712) ％,P ＜ 0.05].Conclusion PCI might significantly suppress the growth of intracranial metastasis of murine melanoma through inhibiting tumor non-spouting angiogenesis.Further investigations of the mechanism are warranted.