牛蒡子苷元对大鼠脑胶质瘤的作用及初步作用机制探讨  

Effects and primary mechanism of arctigenin in C6 rat glioma

作　　者：苏勤勇 李晓梅 姚景春 王平平 张贵民 

机构地区：[1]鲁南制药集团股份有限公司,中药制药共性技术国家重点实验室,山东临沂276006

出　　处：《中国药理学通报》2015年第6期805-809,共5页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划(973计划)资助项目(No2012CB724001)

摘　　要：目的观察牛蒡子苷元对大鼠C6胶质瘤的作用及作用机制的研究。同时探讨牛蒡子苷元与替莫唑胺合用对脑胶质瘤是否有协同作用。方法采用脑内注射C6胶质瘤细胞建立大鼠C6胶质瘤模型;牛蒡子苷元连续皮下给药15 d,替莫唑胺从d 5开始给药,连续灌胃给药5 d;测量肿瘤的长短径,计算肿瘤体积;采用免疫组化方法检测脑瘤组织中GFAP、PCNA和CD40的表达。结果与模型组相比,牛蒡子苷元均能明显降低大鼠C6胶质瘤的肿瘤体积(P<0.05),给予牛蒡子苷元可使脑胶质瘤大鼠的PCNA和CD40表达明显降低(P<0.05),GFAP表达明显升高(P<0.05);牛蒡子苷元与替莫唑胺合用能明显减少脑胶质瘤大鼠的肿瘤体积(P<0.01),其肿瘤抑制率均高于单独牛蒡子苷元和替莫唑胺;与模型组相比,联合用药组的PCNA和CD40表达均明显降低(P<0.05),GFAP明显升高(P<0.05),均好于单独用药。结论牛蒡子苷元能明显抑制大鼠C6胶质瘤生长,并且与替莫唑胺合用具有协同作用,作用机制与影响脑胶质瘤相关蛋白(PCNA和GFAP)表达和调节机体免疫(抑制CD40表达)相关,为牛蒡子苷元上报新药提供临床前药理试验支持。Aim To observe the effect and primary mechanism of arctigenin （ ARG） in C6 rat glioma. At the same time, to investigate the effect of ARG com-bined with temozolomide. Methods C6 glioma rat model was established, and 90 rats were divided into six groups, which were subcutaneously administered with model, low and high ARG （0. 05 and 0. 1 mg· kg^-1 , sc） , temozolomide （20 mg·kg^-1 , p. o. ） , low ARG combined with temozolomide（TMZ / ARG 0. 05） and high ARG combined with temozolomide （ TMZ /ARG 0. 1 ） . The tumor specimens of brain were col-lected after tumor graft. Proliferating cell nuclear anti-gen （ PCNA ） , glial fibrillary acidic protein （ GFAP ） and CD40 in tumor specimens were determined by im-munohistochemistry. Results ① Compared with the model group, the tumor sizes of rats in the arctigenin treatment groups were decreased （ P〈0. 05 ） . ②ARG significantly decreased PCNA and CD40 expression （ P〈0. 05 ） and increased GFAP expression （ P〈0. 05 ） .③ Compared with model group, arctigenin combined with temozolomide decreased the tumor sizes （ P 〈0. 01 ） , and the tumor inhibition rate was higher than that of the arctigenin and temozolomide. At the same time, arctigenin combined with temozolomide de-creased PCNA and CD40 expression （ P 〈0. 01 ） and increased GFAP expression （ P 〈0. 05 ） , which was better than arctigenin and temozolomide. Conclusion Arctigenin inhibits rat glioma growth, and synergizes with temozolomide, which may be associated with in-hibiting PCNA and CD40 expression and strengthening GFAP expression.

关 键 词：脑胶质瘤 牛蒡子苷元 替莫唑胺 PCNA GFAP CD40 新药 

分 类 号：R-332[医药卫生] R284.1