脑瘤一号方联合替莫唑胺对裸鼠脑胶质瘤模型MGMT、Bax和Bcl-2蛋白表达的影响  

Effects of Naoliu Decoction I Combined with Temozolomide on Expression of MGMT,Bax and Bcl-2 Proteins in Glioma Nude Mice

作　　者：袁洁 张珏[1] 费智敏[1] YUAN Jie;ZHANG Jue;FEI Zhi-min(Department of Neurosurgery,Shuguang Hospital,Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai(200120))

机构地区：[1]上海中医药大学附属曙光医院神经外科

出　　处：《中国中西医结合杂志》2019年第12期1477-1482,共6页Chinese Journal of Integrated Traditional and Western Medicine

摘　　要：目的观察脑瘤一号方联合替莫唑胺(TMZ)对脑胶质瘤模型O^6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、Bax和Bcl-2蛋白表达的影响。方法经荧光素mcherry转染的人神经胶质瘤U87细胞(U87MG-Luc),注射于BALB/c裸鼠纹状体,建立裸鼠脑胶质瘤原位模型,成瘤裸鼠(荧光量≥1×105)24只随机分为模型组(生理盐水0.3mL)、TMZ组(TMZ 50mg/kg)、脑瘤一号方组(脑瘤一号方32.125 mg/g)和联合组(TMZ50 mg/kg+脑瘤一号方32.125 mg/g),每组6只,连续灌胃12天,每3天检测1次裸鼠体重、肿瘤体积,给药结束后取脑组织,HE染色检测瘤块组织病理,Western Blot检测MGMT、促凋亡因子Bax和抗凋亡因子Bcl-2水平。结果与模型组比较,TMZ组、脑瘤一号方组和联合组肿瘤体积减少(P<0.05),TMZ组肿瘤组织MGMT表达升高(P<0.05),联合组Bax表达及Bax/Bcl-2升高(P<0.05),抗凋亡因子Bcl-2表达水平降低(P<0.05)。与TMZ组比较,联合组MGMT及Bcl-2表达降低(P<0.05),Bax表达及Bax/Bcl升高(P<0.05)。结论脑瘤一号方组和联合组均表现出有效的抗肿瘤作用。脑瘤一号方联合TMZ治疗胶质瘤能降低TMZ副作用,下调MGMT表达缓解胶质瘤细胞对TMZ的耐药性,同时上调Bax和下调Bcl-2表达,促进肿瘤细胞凋亡。Objective To evaluate the effects of Naoliu Decoction I(ND I) combined with temozolomide(TMZ) on the expression of MGMT,Bax and Bcl-2 in the glioma mice model.Methods The human glioma U87 cells transfected by fluorescein mcherry(U87 MG-Luc) were injected into the striatum of BALB/c nude mice to establish glioma model in nude mice.The 24 nude mice with glioma(fluorescence≥1×10~5) were randomly divided into model group(saline 0.3 mL),TMZ group(TMZ 50 mg/kg),ND I group(ND I 32.125 mg/g) and combination group(TMZ50 mg/kg+ND I 32.125 mg/g),six rats in each group,and they were administrated by gavage for 12 successive days.The body weight and tumor volume were measured every 3 days during the experiment.Brain tissue was taken after administration,and the pathology of tumor were detected by HE staining.Western Blot was used to detect O^6-methylguanine-DNA methyltransferase(MGMT),pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2.Results Compared with the model group,the tumor volume of the TMZ group,the ND I group and combination group were significantly decreased(P<0.05).The expression of MGMT in the TMZ group was increased(P<0.05).The expression of Bax and Bax/Bcl-2 in the combination group was increased(P <0.05),meanwhile the expression level of anti-apoptotic factor Bcl-2 was decreased(P <0.05).Compared with the TMZ group,the expression of MGMT and Bcl-2 in the combined group were decreased(P <0.05),Bax and Bax/Bcl-2 expression were increased(P <0.05).Conclusions Both the ND-1 group and the combined group showed an effective anti-tumor effect on the glioma tumor mice model.ND-I combined with TMZ can reduce the side effects,alleviate the resistance of glioma cells to TMZ by down-regulating the expression of MGMT,promote the apoptosis of tumor cells up-regulating Bax and down-regulating the expression of Bcl-2.

关 键 词：脑胶质瘤 脑瘤一号方 替莫唑胺 耐药性 O^6-甲基鸟嘌呤-DNA甲基转移酶 

分 类 号：R73[医药卫生—肿瘤]