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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 preventive effect of tolfenamic acid on colorectal cancer in rats. Methods Wistar clean-grade rats were selected as experimental subjects. Random number table was randomly divided into negative control group, dimethylhydrazine (DMH) induced cancer group, tolfenamic acid (TA) control group and experimental group , 40 rats in each group. The negative control group was injected subcutaneously with normal saline. The rats in DMH group were injected subcutaneously with dimethyl hydrazine to establish the model of colorectal cancer in rats. Toxofenac acid injection was given to the control group of tolfenamic acid. The experimental groups were treated with 0.1 and 0.2 ml / kg of tolfenamic acid. The rats were given 0.1 and 0.2 ml / kg of tolfenamic acid injection simultaneously with subcutaneous injection of dimethyl hydrazine solution and injected intraperitoneally once / d At week 32, the rats were dissected at 12 and 32 weeks respectively to observe the general state of the rats and the tumorigenesis. The morphological and toxicological effects of the tolofenac control group for 32 weeks were evaluated. Results At 12 weeks, no tumor was found in each group of rats. At 32 weeks, 20 of DMH-induced cancers and 19 of 19 carcinomas developed a rate of 95.0%. Twenty rats of 0.1 ml / kg of tolfenamic acid group, 9 produced tumors with a rate of 45.0%; 20 rats with 0.2 ml / kg tolfenamic acid group and 3 tumors with a rate of 15.0% had statistical significance compared with those with DMH (P <0.05). All the rats in the negative control group and the tolfenamic acid control group did not produce tumors at the 32nd week of experiment. Tumor size was measured and found that the experimental group of tumor diameter of 1 ~ 7 mm, generally lower than the DMH induced cancer group. Tofenamic acid control group, all rats in general good condition, did not appear to die after 32 weeks of administration, body weight and negative control group, the difference was not statistically significant, 2 rats appeared intraperitoneal administration 30 min after the occurrence of tremor, tail Uplift symptoms, duodenal ulcer occurred in 1 rat, macroscopic observation of liver, kidney, heart and other important tissues and organs, did not find any proliferation of tissue. Conclusion Toxophenone has antagonistic effect on dimethyl hydrazine-induced colorectal cancer in rats.