HIFU联合化疗对裸鼠皮下胶质瘤细胞凋亡及增殖的影响研究

Effect of HIFU combined with chemotherapy on apoptosis and proliferation of glioma cell in nude mice

目的:探讨高强度聚焦超声(High intensity focused ultrosound,HIFU)联合化疗对裸鼠皮下胶质瘤靶区周围细胞凋亡和增殖的影响。方法:建立人(U251)胶质瘤移植模型,随机分入3组,局部分别行单HIFU治疗、单盐酸尼莫司汀(Nimustine,ACNU)及HIFU联合ACNU治疗。治疗24 h后切取肿瘤组织,行HE染色观察组织病理变化,免疫组织化学法检测增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)的表达和TUNEL法检测细胞凋亡。治疗7 d后分别测量3组瘤块体积。结果:HIFU联合化疗组靶区周围组织凋亡细胞数较单HIFU组及单化疗组高(P<0.01);而PCNA阳性细胞数较后两者降低(P<0.01)。联合治疗组肿瘤体积较单HIFU组及单化疗组缩小(P<0.01)。结论:HIFU治疗及化疗在胶质瘤的治疗中具有协同作用。HIFU联合化疗能明显提高HIFU治疗疗效,诱导靶区周围胶质瘤细胞凋亡并抑制其增殖发挥抗肿瘤作用,有利于胶质瘤的治疗。

Objective：To explore the changes of cell apoptosis and proliferation in the periphery of the target area on glioma subcutaneous transplanted model in nude mice treated with high inensity focused ultrasound （HIFU） in combination with chemotherapy. Methods： Experimental nude mice of subcutaneous transplanted models with human glioma （U251） was established. These nude mice bearing subcutaneous human neuron-gliocytoma xenografts were divided into three groups randomly, HIFU in combination with ACNU （Nimustine） adjuvant themotherapy group,single chemotherapy group and single HIFU group. 24 hours after tumors were treated,the pathological characteristics,apoptosis and proliferating cell nuclear antigen（PCNA ） in tumor tissues were tested by HE staining examination, TdT-me diated UTP nick end labeling （TUNEL） and immunohistochemical staining respectively. 7 days later,the volume of the xenografts was measured. Results： After HIFU ablation ,in the periphery of the target area,the percentage of PCNA in the HIFU in combination with adjuvant chemotherapy group was significantly less than that in single chemotherapy group and single HIFU group （P〈0.01） and the apoptosis cells were more than these in the last two groups（P〈0.01 ）. The volume of tumor tissues in HIFU in combination with ACNU group was smaller than that in single chemotherapy group and single HIFU group（P〈0.01 ）. Conclusion：There were marked synergstic effects of both HIFU ablation and chemotherapy on U251 glioma in nude mice. In the periphery of the target area, HIFU in combination with adjuvant chemotherapy could enhance the HIFU therapeutic effects obviously,and also induce U25 l cell apoptosis and restrain its proliferation in glioma, thus it would promote the therapeutic efficacy for glioma.