脑胶质瘤动物模型的建立及外源性P21～（WAFI/CIP1）基因治疗胶质瘤的实验研究
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摘要
脑胶质瘤是神经系统最常见的恶性肿瘤。长期以来，由于没有一种简单有效的肿瘤动物模型，使得对其发生、发展机制的研究受到极大影响。另外，在胶质瘤的治疗方面，尽管目前采用了手术、化疗、放疗等综合治疗措施，其治愈率仍很低，复发率、伤残率及死亡率仍很高。因而建立理想的胶质瘤动物模型及探索有效的胶质瘤治疗途径，对该肿瘤的研究有着极其重要意义。
本课题在前人研究的基础上，首先应用乙基-N-亚硝基脲和大鼠C_6胶质瘤细胞，探讨了化学药物诱发胶质瘤模型和细胞同种异植胶质瘤模型的可行性，同时研究了抑癌基因P21~(WAF1/CIP1)在胶质瘤组织中的表达，及其对胶质瘤细胞生长的影响，为P21~(WAF1/CIP1)基因治疗胶质瘤的临床应用研究奠定了理论基础。主要研究内容和结果如下：
第一部分 脑胶质瘤动物模型的建立
1．孕18-20天SD大鼠，通过尾静脉穿刺注入乙基-N-亚硝基脲(NNEU，50和70mg／kg)，结果86.49％(32／37)的子一代火鼠诱发产生神经系统肿瘤，其中约1／3肉眼可见，2／3为镜下所见：肿瘤大部分分布在脑(61.1％)和脊髓(25.0％)，小部分分布在外周神经(包括颅神经和脊神经)：肿瘤的病理类型主要是胶质瘤(77.8％)，其次是神经鞘瘤和脑膜瘤。肿瘤的形态特征：位于皮层下白质内，呈园形或类园形，灰白色胶胨状，边界清晰：光镜下可见肿
Glioma is one of the most common malignant tumors in the central nervous system. Since there has not been a simple and effective glioma animal model, research on the mechanism of occurrence and development of glioma has been seriously affected. In management of glioma, despit of comprehensive adoption of measures of operation, chemotherapy, radiotherapy and even biotherapy, low cure rate, high death rate, and high recurrence and disabling rate remain. Therefore, establishment of an ideal glioma animal model and discovery of an effective cure for glioma are of utmost significance to study of the tumor.
This paper, based on the previous studies, is intended to establish a chemical agent induced glioma model and a syngeneic transplantation glioma model using N-nitrosoethylurea and the rat's C_6 glioma cells, and to study expression of suppressor gene P21~(WAF1/CIP1) in tissues of glioma and its effects on the growth of the tumor cells so as to provide a theoretical basis for clinical application of P21~(WAF1/CIP1) to management of glioma.
Part I Establishment of brain tumor animal model
1. The Sprague-Dauley rats were inoculated with a single dose of 50 or 70mg/kg of N-Nitrosiethylurea(NNEU) on the 18-20th days of gestation. Tumors developed in the nervous system of about 86.49%(32/37) of
本课题在前人研究的基础上，首先应用乙基-N-亚硝基脲和大鼠C_6胶质瘤细胞，探讨了化学药物诱发胶质瘤模型和细胞同种异植胶质瘤模型的可行性，同时研究了抑癌基因P21~(WAF1/CIP1)在胶质瘤组织中的表达，及其对胶质瘤细胞生长的影响，为P21~(WAF1/CIP1)基因治疗胶质瘤的临床应用研究奠定了理论基础。主要研究内容和结果如下：
第一部分 脑胶质瘤动物模型的建立
1．孕18-20天SD大鼠，通过尾静脉穿刺注入乙基-N-亚硝基脲(NNEU，50和70mg／kg)，结果86.49％(32／37)的子一代火鼠诱发产生神经系统肿瘤，其中约1／3肉眼可见，2／3为镜下所见：肿瘤大部分分布在脑(61.1％)和脊髓(25.0％)，小部分分布在外周神经(包括颅神经和脊神经)：肿瘤的病理类型主要是胶质瘤(77.8％)，其次是神经鞘瘤和脑膜瘤。肿瘤的形态特征：位于皮层下白质内，呈园形或类园形，灰白色胶胨状，边界清晰：光镜下可见肿
Glioma is one of the most common malignant tumors in the central nervous system. Since there has not been a simple and effective glioma animal model, research on the mechanism of occurrence and development of glioma has been seriously affected. In management of glioma, despit of comprehensive adoption of measures of operation, chemotherapy, radiotherapy and even biotherapy, low cure rate, high death rate, and high recurrence and disabling rate remain. Therefore, establishment of an ideal glioma animal model and discovery of an effective cure for glioma are of utmost significance to study of the tumor.
This paper, based on the previous studies, is intended to establish a chemical agent induced glioma model and a syngeneic transplantation glioma model using N-nitrosoethylurea and the rat's C_6 glioma cells, and to study expression of suppressor gene P21~(WAF1/CIP1) in tissues of glioma and its effects on the growth of the tumor cells so as to provide a theoretical basis for clinical application of P21~(WAF1/CIP1) to management of glioma.
Part I Establishment of brain tumor animal model
1. The Sprague-Dauley rats were inoculated with a single dose of 50 or 70mg/kg of N-Nitrosiethylurea(NNEU) on the 18-20th days of gestation. Tumors developed in the nervous system of about 86.49%(32/37) of
引文
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