三氧化二砷脂质体治疗大鼠_6脑胶质瘤的实验研究

Experimental study of As_2O_3 liposomes for the treatment of C_6 glioma in rats

目的研究三氧化二砷(As_2O_3)脂质体对荷瘤大鼠血脑屏障(BBB)的透过率及其对大鼠脑胶质瘤的生长抑制作用。方法应用超声薄膜分散法制备As_2O_3脂质体,检测其包封率;建立大鼠脑胶质瘤模型,分别给予As_2O_3脂质体和As_2O_3,应用原子荧光法检测给药后大鼠脑组织中的砷浓度,以判定其对血脑屏障的透过性,并与给予生理盐水的对照组相比,从电镜、TUNNEL、MRI影像及大鼠的生存状态等方面研究As_2O_3脂质体对C_6胶质瘤的影响。结果 As_2O_3脂质体组砷的血脑屏障透过性明显提高,电镜及TUNEL法检测示肿瘤细胞凋亡率(20.03%)高于其他2组(3.92%、4.09%);大鼠中位生存时间(70d)优于生理盐水组(21d)和As_2O_3组(23d)。结论 As_2O_3脂质体可以明显提高鼠脑内As_2O_3浓度,并能诱导胶质瘤细胞的凋亡,抑制大鼠脑胶质瘤的生长,从而延长荷瘤大鼠的生存时间。

Objective To investigate the permeation rate of As 2 O3 liposomes passing blood brain barrier (BBB) in tumor‐bearing rats and its inhibition effect on the C 6 glioma growth in vivo.Methods The As2 O3 liposomes were developed by film‐ul‐trasonic wave dispersion method and the encapsulation efficiency was performed. Then all rats were intravenously injected by As2 O3 liposomes and As2 O3 respectively after successfully establishing the glioma models in rats. After that ,As2 O3 concentra‐tion of brain tissue was measured using atomic fluorescence technique to assess permeability of blood brain barrier . Compared with controls injected by normal saline ,we studied the effect of As2 O3 liposomes on C6 glioma from the following aspects inclu‐ding electron microscopy ,TUNNEL staining ,Magnetic Resonance Imaging (MRI) and the survival condition. Results The As2 O3 liposomes could obviously facilitate permeability of blood brain barrier. The results of electronic microscopic analysis and TUNNEL staining showed that the apoptosis rate (20.03% ) of tumor cells in As2 O3 liposomes group was much higher than that in the other two groups (3.92% ,4.09% ). As2 O3 liposomes group had longer median survival time of 70 days than 21 days in the saline group and 23 days in As2 O3 group.Conclusion The As2 O3 liposomes can significantly improve the As2 O3 concentration of rats'brain ,and can induce apoptosis in glioma cells and suppress intracranial tumor growth and prolong the life span of tumor‐bearing rats.