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目的:腺相关病毒(adeno-associated virus,AAV)介导的重组血管抑素(angiostatin,AS)联合应用雷公藤红素(celastrol)治疗大鼠颅内C6胶质瘤,观察其对肿瘤体积、新生血管密度及肿瘤细胞凋亡的影响,探讨抗血管生成重组基因联合雷公藤红素对胶质瘤治疗的前景。方法:建立颅内原位荷C6脑胶质瘤大鼠模型,7d后随机分为4组,分别给予0.9%氯化钠溶液(作为对照)、AAV-AS、雷公藤红素及两者联合用药。每隔7d行头部强化MRI检查,计算肿瘤体积。于22d后处死动物,检测AS蛋白表达、血管密度及肿瘤细胞凋亡情况。结果:联合治疗组及AAV-AS治疗组均检测到AS蛋白表达,证实基因转导成功。联合治疗组第22天时肿瘤体积、血管密度和凋亡指数均与对照组、雷公藤红素组及AAV-AS治疗组相比差异有统计学意义(P<0.05),联合治疗可以抑制肿瘤生长,降低新生血管密度,促进肿瘤细胞凋亡。结论:基因治疗联合雷公藤红素可通过抑制胶质瘤血管生成而抑制肿瘤生长;两者联合应用具有协同作用,可弥补两者单独应用的不足之处。
OBJECTIVE: AAV-mediated angiostatin (AS) combined with celastrol in the treatment of intracranial C6 glioma in rats and its effect on tumor volume, Neovascularization density and tumor cell apoptosis, and explore the prospect of anti-angiogenesis recombinant gene combined with tripterine on glioma. Methods: The rat model of C6 glioma was established by intracranial injection of C6 glioma. After 7 days, rats were randomly divided into 4 groups: 0.9% sodium chloride solution (control), AAV-AS, tripterine and their combination Medication. Head MRI was performed every 7 days to calculate the tumor volume. Animals were sacrificed after 22 days to detect the expression of AS protein, vascular density and tumor cell apoptosis. Results: AS protein expression was detected in the combination therapy group and AAV-AS treatment group, which confirmed the successful gene transduction. The tumor volume, the density of blood vessels and the apoptotic index in the combined treatment group at day 22 were significantly different from those in the control group, tripterine group and AAV-AS treatment group (P <0.05), and the combination therapy could inhibit tumor growth , Reduce neovascular density and promote tumor cell apoptosis. Conclusion: Gene therapy combined with tripterine inhibits tumor growth by inhibiting glioma angiogenesis. The combination of the two can have synergetic effects and can make up for the shortcomings of the two alone.