摘要
目的探讨放射性粒子125I在动物体内抗人脑胶质瘤的效果及其作用机制。方法建立人胶质瘤的动物模型,瘤内植入放射性粒子125I,观察肿瘤生长情况,在电镜下观察其超微结构的变化,采用TUNEL技术检测肿瘤组织的凋亡情况,流式细胞仪检测Bax/Bcl-2的表达,并应用免疫组化染色检测血管密度和VEGF、bFGF的表达。结果成功建立了人胶质瘤细胞U251的动物模型,植入放射性粒子125I后,胶质瘤生长较对照组明显受到抑制(P<0.05,P<0.01),电镜下可呈现核断裂、染色质边聚等细胞凋亡的形态特征。检测显示:和对照组相比,肿瘤组织的Bax/Bcl-2(1.88±0.47vs1.11±0.52,P<0.01)和组织凋亡率的IHS评分(3.64±0.89vs0.81±0.45,P<0.01)明显增高;肿瘤组织的微血管密度IHS评分(1.40±0.55vs3.23±0.87,P<0.01)、VEGF的IHS评分(1.58±0.55vs4.19±0.45,P<0.01)和bFGF的IHS评分(2.44±0.89vs3.52±0.79,P<0.05)明显降低。结论放射性粒子125I对在体人胶质瘤U251有明确的抑制作用,促进瘤细胞凋亡和降低瘤组织微血管密度可能是其主要作用机制。
Objective To investigate the efficacy of 125I in treatment of nude mice implanted with human glioma cell line U251 and the related mechanism. Methods The animal models of human malignant glioma were established with nude mice. 125I was implanted into tumors and the tumor growth was observed. The ultrastructural change was observed by electron microscopy. The apoptosis of the tumor tissue was examined by in situ end -labelling technique; expression of Bax/Bcl -2 was detected by flow cytometer. Blood vessel density and expression of VEGF,bFGF were observed by immunohistochemistry. Results Nude mouse models of human malignant glioma were successfully established. Compared with control group,125I significantly inhibited tumor growth in nude mice（ P 〈 0. 05,P 〈 0. 01 ）. Electron microscopy demonstrated that the tumor cells displayed apoptosis characteristics such as nuclear fragmentation,margination of condensed chromatin. The expression of Bax/Bcl-2 in the 125I implanting group （ 1.88 ± 0. 47） was significantly increased compared with that in the control group （ 1. 11 ± 0. 52,P 〈 0. 01） ,and the apoptosis rate of tumor tissues in the 125 I implanting group （ 3. 64 ± 0. 89） was significantly higher （ 0. 81 ± 0. 45,P 〈 0. 01）. The blood vessel density in the 125 I implanting group was significantly lower than that in the control group （ 1. 40 ± 0. 55 vs 3. 23 ± 0. 87,P 〈 0. 01）. The expression of VEGF,bFGF in 125 I implanting group was significantly lower than that in the control group （ 1. 58 ± 0. 55 vs 4. 19 ± 0. 45 for VEGF,P 〈 0. 01; 2. 44 ± 0. 89 vs 3. 52 ± 0. 79 for bFGF,P 〈 0. 05）. Conclusion 125 I has prominent inhibitory effect against human gliomas,and the main mechanism might be the promotion of apoptosis and decrease of blood vessel density.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2010年第1期46-50,共5页
Academic Journal of Second Military Medical University
基金
河北省自然科学基金(C2004000671)~~
