海藻玉壶汤对小鼠胸腺淋巴瘤生长抑制的机制研究  

Study of Haizao Yuhu Decoction on Growth Inhibitory Mechanism for Thymic Lymphoma in Mice

作　　者：王业生[1,2,3] 杜钢军[2] 孙玲[1] 张亚平[2] 孙婷[2] 宋永平[3] 

机构地区：[1]郑州大学第一附属医院血液科,郑州450000 [2]河南大学药学院药物研究所,河南开封475004 [3]河南省肿瘤医院血液科,郑州450000

出　　处：《中国实验方剂学杂志》2013年第2期191-195,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81173094);河南省科技厅重点攻关项目(112101310308);河南大学省部共建项目(SBGJ090704);河南省高校青年骨干教师项目(2010GGJS-025)

摘　　要：目的:研究海藻玉壶汤对小鼠胸腺淋巴瘤生长抑制的机制。方法:将N-甲基亚硝基脲诱导的胸腺淋巴瘤经裸小鼠移植成功后接种到小鼠皮下建立小鼠胸腺淋巴瘤移植模型,采用近期疗效和远期预后评价抗肿瘤效果。近期疗效,在模型建立同时用海藻玉壶汤20 g.kg-1ig给药,每日1次,连续5周,末次给药后次日检测肿瘤大小、肿瘤血流速度、瘤组织黏度、瘤组织基质金属蛋白酶9(MMP-9)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶抑制物1(TIMP-1)、转化生长因子β1(TGF-β1)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、Fas含量、探讨其肿瘤生长抑制机制。远期预后,将海藻玉壶汤按人等效日剂量加入到小鼠24 h量的饮水中,每日更换1次,直至实验结束,记录每只小鼠的存活周数。另以治疗肿瘤剂量海藻玉壶汤给小鼠连续灌胃2周后分离小鼠血清,将血清作用于小鼠胚肺成纤维细胞L929及小鼠脾淋巴细胞,检测含药血清对细胞增殖和对L929成纤维细胞Ⅰ-Ⅳ胶原分泌的影响。结果:近期治疗效果评价,模型组小鼠瘤重为(2.48±0.42)g,海藻玉壶汤20 g.kg-1组小鼠瘤重为(0.79±0.48)g,肿瘤抑制率达68.1%。远期预后评价,未治疗荷瘤小鼠中位存活时间为11周,而经海藻玉壶汤治疗的小鼠中位存活时间为26周。机制研究发现,海藻玉壶汤能降低肿瘤血流速度、瘤组织黏度,降低TIMP-1,TGF-β1,VEGF,bFGF含量,升高瘤组织MMP-9,MMP-2和Fas含量。另外,海藻玉壶汤含药血清能促进小鼠脾淋巴细胞增殖,抑制L929成纤维细胞增殖及Ⅰ-Ⅳ胶原分泌。结论:海藻玉壶汤能阻止小鼠胸腺淋巴瘤生长,其机制与调节肿瘤微环境中基质降解、细胞凋亡和免疫增强有关。Objective： To observe effect of Haizao Yuhu decoction （HYD） on growth inhibitory mechanism for thymie lymphoma in mice. Method： The implantation model of thymic lymphoma in mice was established by subcutaneous injection of thymic lymphoma ceils from nude mouse xenograft tumor induced by N- methyl nitroso urea （MNU）. Antitumor of HYD was evaluated by recent curative effect and forward prognosis. In recent curative effect, HYD ig 20 g ·kg-1 was used to treat mouse once daily for five weeks. Next day after the end of dosage, antitumor of HYD and its growth inhibitory mechanism for thymic lymphoma were investigated by assay of tumor size, blood flow velocity, tissue viscosity, matrix metalloproteinases-2 （ MMP-2 ）, matrix metalloproteinases-9 （MMP-9）, tissue inhibitor of metalloproteinases （TIMP-1） , transforming growth factor-β（TGF-β1）, vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF）, and Fas. In forward prognosis, HYD po at equivalent dose in drinking water was used to treat mouse once daily untill the end experiment. Life span was analyzed. In addition, the medicated serum from mice received intragastric HYD for two weeks was prepared and used to treat mouse embryonic lung fibroblast （L929 cells） and spleen lymphocyte and observe its effect on cell proliferation and collagen I -IV secretion in L929 cells. Result： In curative recent effect, the tumor weight in model group is （2.48 ±0.42） g while it was （0.79±0.48） g in HYD group, tumor inhibitory rate of HYD was 68.1%. In forward prognosis, median life span in model group and HYD group were 11 weeks and 26 weeks respectively. In mechanism study, HYD could reduce blood flow velocity, tissue viscosity, TIMP-1, TGF-β1, VEGF and bFGF, increase MMP-2, MMP-9 and Fas. In addition, HYD could promote Spleen lymphocyte proliferation and inhibit proliferation and collagen I -IV secretion in L929 cells. Conclusion： HYD could suppress growth and metastasis of thymic lymphoma in mice, its

关 键 词：海藻玉壶汤 胸腺淋巴瘤 基质降解 细胞凋亡 免疫增强 

分 类 号：R285.5[医药卫生—中药学]