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目的 明确IGF 1在脑肿瘤发生发展中的作用并为基因治疗优选靶的。方法 采用Wistar大鼠C6脑胶质瘤模型进行反义IGF 1基因治疗 ,通过MRI及病理活检等手段 ,动态观察、分析各时限治疗组与对照组动物 (每组 10只 )肿瘤的差别。结果 (1)颅内种植肿瘤后 ,反义治疗组肿瘤不断减小至 8周后几乎完全消失 ,动物生存期超过 80天的观察期 ,对照组均因肿瘤增大在 2周前后死亡 ;(2 )治疗组肿瘤相对于同时限对照组者凋亡细胞、淋巴细胞浸润增加 ;IGF 1表达、细胞增殖活性有所下降。结论 反义IGF 1基因治疗能有效抑制大鼠体内胶质瘤的恶性进展 ,IGF 1表达减少使细胞增殖活性下降和免疫系统攻击增强可能是治疗组肿瘤消失的双重原因
Objective To clarify the role of IGF-1 in the development of brain tumors and to optimize targets for gene therapy. Methods Wistar rat C6 glioma model was used to treat the antisense IGF1 gene. The dynamic changes of the gene expression were observed by MRI and pathological biopsy. The differences of the tumors between the treatment group and the control group (10 mice in each group) were analyzed. Results (1) After the tumor was implanted in the brain, the tumor in the antisense treatment group decreased to almost disappear after 8 weeks and the observation period in which the animal survived more than 80 days. The control group both died before and after 2 weeks of tumor enlargement. 2) Compared with the same time-limited control group, tumor cells in treatment group showed increased lymphocyte infiltration and decreased IGF-1 expression and cell proliferation activity. Conclusion Antisense IGF-1 gene therapy can effectively inhibit the malignant progression of glioma in rats. Decreased IGF-1 expression leads to the decrease of cell proliferation activity and the increase of immune system attack, which may be the dual reason of tumor disappearance in the treatment group