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目的:通过苯醋酸对脑胶质瘤小鼠模型的诱导治疗,观察治疗后肿瘤细胞的变化,以评估其在体内治疗恶性脑肿瘤的效果。方法:将G422鼠脑胶质瘤细胞移植到昆明鼠(n=80)脑内,并将其平均分为5组。其中3组为苯醋酸钠用药组,分别用1200、800、400mg·kg1·d1,自移植后的当天开始用药,连续用药14d;对照组用同样的方法注射等量的盐水;另一组为卡氮芥(BCNU)组,20mg·kg1仅1次注射。治疗结束后处死小鼠,行病理、电镜和毒性观察以及流式细胞仪检查,以确定肿瘤细胞的增殖状态。结果:用苯醋酸治疗的小鼠生存期均有延长(P<0.05),而没有反应。BCNU组的生命延长期和用苯醋酸治疗的中剂量组相同。病理和电镜观察显示:用苯醋酸处理的小鼠肿瘤细胞有明显的细胞肥大和粗面内质网的机化,表示有细胞的分化。流式细胞仪检测显示,苯醋酸可以使G422细胞的分化阻滞在G1期。结论:醋酸钠通过抑制蛋白的戊乙烯化或其它机制,而达到抑制肿瘤细胞增殖和诱导分化的作用,可以作为治疗恶性胶质瘤或其它恶性肿瘤的安全有效的新药。
OBJECTIVE: To observe the effect of phenylacetate on glioma mouse model and observe the change of tumor cells after treatment to evaluate its effect on treating malignant brain tumor in vivo. Methods: G422 glioma cells were transplanted into Kunming mice (n = 80), and divided into 5 groups equally. The three groups were sodium phenylacetate treatment group, respectively, with 1200,800,400mg · kg -1 d 1, since the day after transplantation began to medication, continuous medication 14d; control group using the same method of injection of the same amount of saline; The other group was BCNU group, 20mg · kg1 only one injection. Mice were sacrificed after treatment, pathological, electron microscopic and toxicological observations and flow cytometry to determine the proliferation of tumor cells. Results: The survival time of mice treated with phenylacetate was prolonged (P <0.05), but no response was observed. The prolongation of life in the BCNU group was the same as in the mid-dose group treated with phenylacetate. Pathology and electron microscopy showed that the tumor cells treated with phenylacetate had obvious cell hypertrophy and mechanization of rough endoplasmic reticulum, which indicated the differentiation of cells. Flow cytometry showed that phenylacetate could block the differentiation of G422 cells in G1 phase. CONCLUSION: Sodium acetate can inhibit the proliferation and differentiation of tumor cells by inhibiting the pentacenezation of protein or other mechanisms. It can be used as a new and safe drug for the treatment of glioblastoma or other malignant tumors.