摘要
目的探索托芬那酸对大鼠大肠癌的预防作用。方法选择Wistar清洁级大鼠作为实验对象,随机数字表法随机分为阴性对照组、二甲基肼(dimethylhydrazine,DMH)诱癌组、托芬那酸(tolfenamic acid,TA)对照组和实验组,每组40只大鼠,阴性对照组给予生理盐水皮下注射;DMH诱癌组给予二甲基肼皮下注射建立大鼠大肠癌模型;托芬那酸对照组单纯给予托芬那酸注射液;实验组分为0.1和0.2 ml/kg托芬那酸组,给予二甲基肼溶液皮下注射的同时分别给予0.1和0.2 ml/kg托芬那酸注射液,腹腔注射,1次/d,连续32周,大鼠分别于12和32周进行解剖,观察大鼠的一般状态以及肿瘤发生情况,并对32周的托芬那酸对照组大鼠的形态以及毒性作用进行评价。结果 12周时,各组大鼠均无肿瘤产生;32周时,DMH诱癌组20只,19只产生肿瘤,发生率为95.0%;0.1 ml/kg托芬那酸组20只大鼠,9只产生肿瘤,发生率为45.0%;0.2 ml/kg托芬那酸组20只大鼠,3只产生肿瘤,发生率为15.0%,与DMH诱癌组相比差异具有统计学意义(P<0.05);阴性对照组和托芬那酸对照组所有大鼠在实验32周时均未产生肿瘤。对肿瘤大小进行测量,发现实验组的肿瘤直径为1~7 mm,普遍低于DMH诱癌组。托芬那酸对照组所有大鼠一般状态良好,给药32周未出现死亡,体质量与阴性对照组对比差异无统计学意义,出现2例大鼠腹腔给药30 min后出现身体震颤、尾巴隆起症状,1例大鼠发生十二指肠溃疡,肉眼观察肝脏、肾脏、心脏等重要组织器官,未发现任何增生组织。结论托芬那酸对二甲基肼诱发的大鼠大肠癌具有拮抗作用。
Objective To explore the antagonistic effect of tolfenamic acid on colon cancer induced by dimethylhydrazine in mice.Methods Wistar mice were randomly divided into negative control group,DMH-induced cancer group,DMH + tolfenamic acid group( the experimental group),tolfenamic acid control group. the negative control group was adminstered subcutaneously normal saline; DMH-induced colon cancer was made by subcutaneous injection of dimethylhydrazine; tolfenamic acid control group was given tolfenamic acid injection; the experimental group was divided into 0. 1,0. 2 ml/kg tolfenamic acid group,given dimethylhydrazine at the same time,subcutaneously given0. 1 and 0. 2 ml/kg tolfenamic acid,respectively,once a day for 32 weeks,all mice euthanized at 12 nd week and 32 nd week were dissected to investigate the incidence of the tumor and the general condition: at 32 nd week,tolfenamic acid control mice were given evaluation of toxicity and general condition. Results At 12 nd week,the all mice were free of tumor; at 32 nd week,in DMH-induced cancer group,19 tumors were observed,the incidence rate was 95%; in 0. 1 ml/kg tolfenamic acid group,9 tumors,the incidence rate 45%; in 0. 2 ml tolfenamic acid/kg group,only 3 the tumors,the incidence rate 15%,and tumor incidence rate in DMH-induced cancer group is significantly higher than in the others( P 〈0. 05); negative control group and tolfenamic acid group mice were no tumor at 32 nd week. The tumor sizes of mice were measured and the tumor diameters of mice in the experimental group were 1 ~ 7 mm,which were generally lower than that in DMH induced cancer group. dimethylhydrazine group mice are in good condition,and no death at 32 nd week,body weight had no significant difference compared with the negative control group,2 cases injected intraperitoneally by Tolfenamic acid appeared body tremor and tail uplift symptoms 30 min after administration; 1 duodenal ulcer,organs,such as liver,kidney,and heart,were also in good condition. Conclusion Tolfenamic acid has preventive effects. on dimethylhydrazine-induced colon cancer in mice.
出处
《毒理学杂志》
CSCD
北大核心
2017年第2期118-122,共5页
Journal of Toxicology
关键词
托芬那酸
二甲基肼
大肠癌
大鼠
防治
Tolfenamic acid
Dimethylhydrazine
Colorectal cancer
Wistar mice
Prevention