扶正增效方放射增敏与肿瘤细胞内O^6-甲基鸟嘌呤DNA甲基转移酶的关系  

The Relationship Between Radiosensitization of Fuzheng-zengxiao Formula and O^6-methylguanine-DNA Methyltransferase

作　　者：黄金昶[1] 王立森 杜新生[2] 王彦刚[3] 高永辉 

机构地区：[1]卫生部中日友好医院,100029 [2]承德医学院附属医院 [3]河北省中医院 [4]山东省枣庄矿业集团中心医院

出　　处：《医学研究通讯》2005年第5期16-20,共5页Bulletin of Medical Research

基　　金：国家自然科学基金资助课题(No.30271653;30371823)

摘　　要：目的探讨扶正增效方放射增敏与肿瘤细胞内 O^6-甲基鸟嘌呤 DNA 甲基转移酶(O^6-MT)关系。方法建立裸鼠人肺腺癌 PAa 模型,分为6组,从接种日始,Ⅱ、Ⅳ、Ⅵ组裸鼠每天灌服0.6g 扶正增效方水煎剂,Ⅰ、Ⅲ组灌服等量无菌生理盐水,35天Ⅴ、Ⅵ组腹腔注射2mg STZ,36天予Ⅲ、Ⅳ、Ⅴ、Ⅵ组瘤体10Gy X 线照射,测瘤体直径、O^6-MT 含量、MGMT 染色及细胞病理学镜检。结果 6组中O^6-MT 含量工组最高,Ⅵ组最少,Ⅳ、Ⅴ、Ⅵ组与Ⅰ组相比差异显著,Ⅳ、Ⅵ组相比差异也显著;MGMT 染色强度变化与 O^6-MT 含量一致。瘤体生长Ⅰ、Ⅱ组瘤体放疗第4天起明显增大,Ⅲ组第6天明显增大,与Ⅰ、Ⅱ组相比增长减慢;Ⅳ、Ⅴ、Ⅵ组瘤体在第4天明显减少,以第Ⅵ组最明显;病理学镜检Ⅲ组见小的散在坏死灶,Ⅳ、Ⅴ组坏死区域较Ⅲ组增加,Ⅳ组与Ⅴ组相似;Ⅵ组坏死区域明显增多增大。通过对 O^6-MT 活性、MGMT 染色强度与病理学镜检、瘤体大小对比,细胞内 O^6-MT 含量与放射敏感性密切相关,O^6-MT 含量低组别放疗效果好。结论 O^6-MT含量决定其放射敏感性,据 O^6-MT 活性高低预测其放射敏感性;扶正增效方放射增敏一个重要途径是抑制 DNA 甲基转移酶活性而实现的。Objective To study the relationship between radiosensitization of Fuzheng-zengxiao Formula and O^0-methylguanine-DNA methyltransferase(O^6-MT). Method Human lung adenocarcinoma(PAa)models were developed in nude mice and then divided into 6 groups as follows:Group Ⅰ:Perfusion of distilled germfree brine, no radiotherapy. Group Ⅱ:Perfusion of Fuzheng-zengxiao Formula decoc- tion, no radiotherapy.Group Ⅲ:Perfusion of distilled germfree brine and radiotherapy.Group Ⅳ:Perfusion of Fuzhengzengxiao Formula decoc- tion and radiotherapy. Group Ⅴ:Injection of STZ into celiac and radiotherapy. Group Ⅵ:Perfusion of Fuzhengzengxiao Formula decoction, in- jection of STZ into celiac and radiotherapy.Fuzheng-zengxiao Formula decoction(0.6g/0.2ml)was perfused per day to nude mice of group Ⅱ、 Ⅳ and Ⅵ from the day inoculating, equate distilled germfree brine was perfused to mice of group Ⅰ、Ⅲ 2mg/0.4ml STZ was injected into celi- ac in group Ⅴ and Ⅵ on day 35, radiotherapy of 10GY X ray was performed to group Ⅲ、Ⅳ、Ⅴ and Ⅵ on day 36. Measure diameter of tu- mor、concentration of 0~6-MT、MGMT coloration and observe cellular pathology under lens. Result The concentration of O^6-MT in group Ⅰ is 0.46±0.09 pmol/mg protein, the highest among Ⅵ groups;the concentration in group Ⅵ is the lowest, 0.21±0.10 pmol/mg protein, the difference between group Ⅳ、group Ⅴ、group Ⅵ and group Ⅰ is obvious, the difference between group Ⅳ and group Ⅵ is noticeable;various intensities of MGMT coloration accord with the concentration of 0~6-MT.The growth of tumor:Accretion of tumor in group Ⅰ and Ⅱ is notable from the 4th day after radiotherapy, so is the group Ⅲ from the 6th day, but more slowly compared with group Ⅰ and Ⅱ;the tumor of group Ⅳ、 Ⅴ、Ⅵ reduced remarkably, especially on 4th day.Pathologic observation under lens:Small dispersed necrotic focuses can be seen in group Ⅲ, in group Ⅳ、Ⅴ necrotic region is much larger, group Ⅳ and Ⅴ are simillar;necrotic re

关 键 词：O^6-甲基鸟嘌呤 DNA甲基转移酶 扶正增效方 放射增敏 细胞内 肿瘤 O^6-MT 放射敏感性 无菌生理盐水 MGMT 细胞病理学 人肺腺癌 方法建立 腹腔注射 x线照射 瘤体直径 差异显著 强度变化 瘤体生长 瘤体大小 含量 PAa 接种日 

分 类 号：R730.2[医药卫生—肿瘤] R735.7[医药卫生—临床医学]