摘要
目的制备替莫唑胺(TMZ)鼻腔脑靶向药物组合,并初步评价其在大鼠C6胶质瘤模型的治疗效果。方法接种C6胶质瘤细胞,得到大鼠胶质瘤模型40只;随机分为4组:空白组、静脉注射TMZ组、口服TMZ组和鼻腔脑靶向药组,每组10只。分别用生理盐水、TMZ静脉注射、灌胃以及鼻腔脑靶向制剂对大鼠C6胶质瘤模型治疗后,观察大鼠的肿瘤体积大小、生存期、病理学的改变。结果 TMZ脑靶向药治疗后肿瘤体积增长明显低于空白组、静脉注射TMZ组和口服TMZ组(12.45±2.49 mm3vs60.16±4.12 mm3,33.17±3.56 mm3,35.16±4.36 mm3,P<0.05)。中位生存期鼻腔脑靶向药组较空白组、静脉注射TMZ组和灌胃TMZ组延长(31.0 d vs 20 d,19 d,21.5 d,P<0.05)。HE染色证实各组大鼠均接种了胶质瘤,TMZ鼻腔脑靶向药组较其他各组PCNA表达减少,凋亡增加。结论 TMZ脑靶向药能抑制胶质瘤肿瘤细胞的生长,或可作为治疗胶质瘤新的有效制剂。
Objective To study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts. Methods Forty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group. Results Magnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45±2.49 mm3 vs 60.16±4.12, 33.17±3.56, and 35.16±4.36 mm3, respectively, P〈0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P〈0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group. Conclusion Intranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2014年第5期631-635,共5页
Journal of Southern Medical University
基金
国家自然科学基金(30970816)~~
关键词
胶质瘤
替莫唑胺
核磁共振成像
脑靶向给药
glioma
temozolomide
magnetic resonance imaging
brain targeting delivery