【作者】 肖刚；

【导师】 霍钢；

【作者基本信息】 重庆医科大学 ， 外科学， 2009， 硕士

【摘要】 目的:以裸鼠皮下人胶质瘤模型为研究平台。对胶质瘤行局部化疗和(或)高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)辐照。HIFU辐照后,观测胶质瘤组织病理、瘤细胞的增殖细胞核抗原和细胞凋亡变化特点以及肿瘤体积变化。探讨HIFU联合化疗在裸鼠皮下人胶质瘤治疗中的作用,为进一步增强HIFU消融作用提供实验基础。方法:对数生长期的U251胶质瘤细胞悬液,接种于15只裸鼠双侧臀部皮下,建立裸鼠皮下人胶质瘤模型,接种后第28天肿瘤最长径约1.0～1.2cm。荷瘤鼠随机分入HIFU治疗组、HIFU联合化疗组以及化疗组。CZF-Ⅱ型超声治疗仪行HIFU辐照,治疗探头频率为9.7 MHz,焦距4.5 mm,最大输出功率5 W焦点处声强2500 w/cm~2。绘制各组胶质瘤生长曲线。治疗24小时后行切取肿瘤组织,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 nuclearantigen,PCNA)的表达和原位末端标记法(TdT-mediated dUTP nick endlabeling,TUNEL)检测细胞凋亡。结果:成瘤率100%,裸鼠皮下人胶质瘤模型建立。HIFU辐照后24小时,HIFU辐照后靶区凝固性坏死形成。联合治疗组靶区周围组织PCNA表达较单HIFU组及单化疗组降低,差异有统计学意义(P＜0.01);联合治疗组靶区周围组织凋亡细胞数较单HIFU组及单化疗组增强,差异有统计学意义(P＜0.01);治疗后7d,联合治疗组肿瘤体积较单HIFU组及单化疗组缩小,差异有统计学意义(P＜0.01)。结论:HIFU联合化疗能提高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。HIFU治疗及化疗在胶质瘤的治疗中具有协同作用。更多还原

【Abstract】 Objective:Human glioma(U251) subcutaneous models in nude mice was set as a research platform.Localized chemotherapy and/or high inensity focused ultrasound(HIFU) ablation were given respectively.After the treatment,the volume of tumors was measured and the pathological characteristics,apoptosis and proliferating cell nuclear antigen(PCNA) in tumor tissues were tested respectively.It mainly focuses the role about the treatment of HIFU combined with chemotherapy on subcutaneous glioma,which provided a new method to enhance HIFU effects.Methods:Logarithmic phase U251 glioma cell suspension was inoculated into the bilateral hip subcutaneous tissue of 15 nude mice, human glioma(U251) subcutaneous models in nude mice was established. 28 days later,the longest diameter of tumors ranged from 1.0 to 1.2 centimeter.These nude mice bearing subcutaneous human neuron-gliocytoma xenografts were divided into three groups randomly,i.e. HIFU in combination with ACNU(Nimustine) adjuvant themotherapy group,single chemotherapy group and single HIFU group.The CZF-Ⅱextracorporeal HIFU with 9.7MHz transducer(focal length:4.5 mm, focal intensity:2 500 W/cm~2) was adopted in the experiment.The growth curves in three groups were mapped.The pathological characteristics,apoptosis and PCNA in tumor tissues were tested by HE staining examination,TdT-mediated UTP nick end labeling(TUNEL) and immunohistochemical staining respectively.Results:Tumor formation rate was 100%,and human glioma(U251) subcutaneous models in nude mice was established.24 hours after HIFU ablation,coagulatied necrosis in the target area was formed.In the periphery of the target area,the percentage of PCNA in the HIFU in combination with chemotherapy group was significantly less than that in single chemotherapy group and single HIFU group(P＜0.01),and the number of apoptosis cells was more than the other two groups(P＜0.01).7 days later,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:In the periphery of the target area,HIFU in combination with adjuvant chemotherapy could enhance the HIFU therapeutic effects obviously,and also induce U251cell apoptosis and restrain its proliferation in glioma,thus it would promote the therapeutic efficacy of glioma.There were marked synergstic effects of both HIFU ablation and chemotherapy on U251 glioma in nude mice.更多还原