多柔比星-纳米肝素介孔硅载药系统对H22移植瘤小鼠的抑瘤作用及肝肾毒性  

Anticancer effects of heparinized mesoporous silicon nanoparticles drug carrier system on H22 tumorbearing mice and its liver and kidney toxicity

作　　者：李瑞芳[1] 吴强[2] 徐新丽[1] 刘鹤阳 付俊敏[1] 冯翔冠 

机构地区：[1]河南科技大学医学院药理学与分子生物学重点实验室,河南洛阳471003 [2]河南大学药学院药剂学教研室,河南开封475004

出　　处：《中国药理学与毒理学杂志》2016年第1期61-67,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：河南科技大学高级别项目培育基金(2015-GJB018)~~

摘　　要：目的研究多柔比星(DOX)-肝素介孔硅载药系统(HMSN)对肝癌H22移植瘤小鼠的抗肿瘤作用及毒性反应。方法建立肝癌H22移植瘤模型,分为模型对照组、HMSN 8 mg·kg^(-1)组、DOX-HMSN4和8 mg·kg^(-1)组及DOX2 mg·kg^(-1)组。DOX每2天1次,其余药物每天1次,尾静脉注射给药,末次给药24 h后,称取瘤重,计算抑瘤率;HE染色观察H22小鼠肿瘤组织的病理改变;光镜下进行白细胞计数,计算胸腺和脾指数;检测血清中肌酐(Scr)、尿素氮(BUN)、谷丙转氨酶(GPT)及谷草转氨酶(GOT)的含量;Western蛋白印迹法检测凋亡蛋白BCL-2,BAX及血管内皮生长因子(VEGF)的表达。结果 HMSN8 mg·kg^(-1)组、DOX-HMSN 4和8 mg·kg^(-1)组及DOX 2 mg·kg^(-1)组对H22小鼠实体瘤的抑瘤率分别为20.5%,40.4%,54.8%及67.5%(P<0.01)。HMSN 8 mg·kg^(-1)组、DOX-HMSN 4和8 mg·kg^(-1)组及DOX2 mg·kg^(-1)组病理观察均可见肿瘤组织大片坏死,出现空泡和胞核溶解。与模型对照组相比,DOX-HMSN 4和8 mg·kg^(-1)组的白细胞计数、胸腺和脾指数无显著变化。DOX-HMSN 4和8 mg·kg^(-1)对H22小鼠的Scr和BUN无明显影响,但能降低其GPT和GOT的水平(P<0.05)。DOX-HMSN 4和8 mg·kg^(-1)组和DOX2mg·kg^(-1)组小鼠的BAX/BCL-2比值由模型对照组的0.49±0.06升高至1.23±0.14,0.79±0.08和1.04±0.14;VEGF表达水平由模型对照组的1.39±0.14降低至0.75±0.08,1.13±0.12和0.94±0.09(P<0.05)。结论 DOX-HMSN 4和8 mg·kg^(-1)能抑制H22移植瘤小鼠实体瘤的生长,其机制可能与诱导肿瘤细胞凋亡及抑制血管生成有关。OBJECTIVE To investigate the antitumor effect and toxicity of doxorubicin-heparinized mesoporous silicon nanoparticles drug carrier system（DOX-HMSN） on H22 hepatoma mice.METHODS An experimental animal model of H22 hepatoma mice was established.Fifty male Kunming mice were divided into five groups：model control group,HMSN 8 mg·kg^（-1） group,DOX-HMSN 4,8 mg·kg^（-1） groups,and DOX 2 mg·kg^（-1）（once every other day） group.Continuous intravenous injection was given once a day for 14 d.Tumor was completely stripped and weighed,and tumor inhibitory rate was determined.Pathological change of tumor tissue was observed by HE staining in H22 mice.White blood cell count was performed and the thymus index and spleen index were calculated.Levels of serum creatinine OBJECTIVE To investigate the antitumor effect and toxicity of doxorubicin-heparinized mesoporous silicon nanoparticles drug carrier system（DOX-HMSN）on H22 hepatoma mice. METHODS An experimental animal model of H22 hepatoma mice was established. Fifty male Kunming mice were divided into five groups：model control group,HMSN 8 mg？kg-1group,DOX-HMSN 4,8 mg？kg-1groups,and DOX 2 mg？kg-1（once every other day）group. Continuous intravenous injection was given once a day for 14 d. Tumor was completely stripped and weighed,and tumor inhibitory rate was determined.Pathological change of tumor tissue was observed by HE staining in H22 mice. White blood cell count was performed and the thymus index and spleen index were calculated. Levels of serum creatinine（Scr）,blood urea nitrogen（BUN）,glutamic pyruvic transaminase（GPT）and glutamic-oxalacetic transaminase（GOT）in serum were determined. BCL-2,BAX and vascular endothelial growth factor（VEGF）expression of tumor tissue were analyzed using Western blot. RESULTS The inhibitory rate of tumor was 20.5%,40.4%,54.8%,and 67.5%,respectively,in HMSN 8 mg？kg-1group,DOX-HMSN 4,8 mg？kg-1group and DOX 2 mg？kg-1group（P〈0.01）. HE results showed that HMSN 8 mg？kg-1,DOXHMSN 4

关 键 词：多柔比星 纳米共轭体 肝癌 

分 类 号：R965[医药卫生—药理学]