苯乙酸钠抑制脑胶质瘤的实验研究

Experimental research on antiglioma effect of sodium phenylacetate

目的 观察苯乙酸钠 (Na PA)治疗 G42 2胶质瘤小鼠的肿瘤细胞变化 ,并探讨其作用机制。方法建立颅内型和肌肉型 G42 2胶质瘤荷瘤鼠模型 ,两种模型各分成 5组。其中 3组为实验组 ,分别予 12 0 0、80 0、40 0 m g/ kg· d的 Na PA治疗。另两组中一组为阳性对照组 ,用卡氮芥 (BCNU)治疗 ,一组为阴性对照组 ,给予生理盐水。两种动物模型于接种瘤细胞 2 4小时后开始用药。阳性对照组腹腔注射 BCNU(2 0 m g/ kg) 1次 ,实验组和阴性对照组分别皮下注射 Na PA和生理盐水 ,共 14天。用药结束后 ,观察颅内型荷瘤鼠的药物毒性反应、小鼠生存期、计算生存率 ,并观察各组胶质瘤组织的病理及超微结构变化。对肌肉型荷瘤鼠 ,测定瘤重抑制率。结果 用 Na PA治疗的荷瘤鼠生存期均有延长 ;Na PA对胶质瘤生长有浓度依赖性抑制作用 ;病理和电镜显示 Na PA治疗后胶质瘤细胞核分裂像减少 ,粗面内质网增多 ,细胞突起出现 ,表示瘤细胞出现分化趋势。结论 Na PA主要通过诱导胶质瘤细胞分化抑制肿瘤生长。

Objective To observe the change of tumor cells on sodium phenylacetate(NaPA) treating G422 glioma mice,and explore its mechanism.Methods Two kinds of mice models(intracranial and muscular G422 glioblasloma cells) were established,and were divided into five groups,among which 3 groups for expe rimental groups,they were received NaPA(1200,800,400 mg/kg·d).In the other two groups,the positive control group was administered BCNU(20 mg/kg) only one time.The negative control group was given saline 24 h later tumor inoculation,these mice bagan to be administered.The experimental group and negative control group were injected NaPA and saline for 14 days respectively.After that,the drug toxicity,the survival period,survival rate of the mice were observed,and the pathology and ultrastructure of glioma in every group were also observed.The muscular tumor mice were sacrificed for measurement of tumor suppression rate.Results NaPA can prolong the life span of the mice with glioma;it has concentration dependent inhibition to glioma proliferation;the pathology and electron microscopy showed the decrease of glioma nuclei fission image treated by NaPA,the increase of rough endoplasmic reliculum and the cell proptosis were found,it demonstrated the tumor cells had differentiation trend.Conclusion NaPA had antitumor effect by inducing glioma cell differentiation and inhibiting the growth of tumor.