藤黄对错配修复基因hMLH1缺失的结直肠肿瘤毒效相关性研究

发布时间：2018-08-29 17:27

【摘要】：目的：藤黄对错配修复基因hMLH1缺失的结直肠肿瘤毒效相关性研究。方法：利用能表达绿色荧光蛋白人结直肠癌HCT116细胞,在无菌环境下通过外科手术建立裸鼠结肠癌模型。分别将HCTll6细胞原位移植成功的荷瘤鼠随机分为6组,每组8只。根据急毒试验中LD50的结果,将藤黄配置成3种高、中、低浓度作为实验组,生理盐水为阴性对照组,5-FU、伊立替康为阳性对照组。藤黄组分别给予高中低三种剂量的藤黄灌胃,1次/日；阳性对照组组分别予5-氟尿嘧啶、伊立替康腹腔灌注,隔日给药1次。每日观察记录动物死亡情况、营养及活动状态,不良反应,在固定时间点分别应用动物活体荧光影像系统测量肿瘤大小,并称体重。治疗25天后,在荧光系统下观察肿瘤血管密度情况,肿瘤大小及转移情况。结果：药物干预后,实验终点0.2g/kg藤黄组肿瘤的平均质量及平均体积均小于对照组(0.52±0.24g vs 1.21±0.63g; 481.0±226.5mm3 vs 956.5±780.1mm3),差异均有统计学意义(P0.05)。盐酸伊立替康组肿瘤的平均质量及平均体积均小于对照组(0.28±0.13g vs 1.21±0.63g; 258.0±126.2mm3 vs 956.5±780.1mm3),差异均有统计学意义(P0.05)。0.1g/kg藤黄组、0.05g/kg藤黄组与5-FU组对照组比较,各组肿瘤的平均质量与体积,无论是各观察点还是实验终点统计结果均无统计学意义(P0.05)。实验结束后观察,在荧光系统下各组荷瘤小鼠体内均有不同程度的胰腺及淋巴结转移,实验过程中(除预实验)各组实验动物均未出现药物相关的不良反应,各实验组的荷瘤裸鼠的个体质量尚未出现明显大的波动。结论：藤黄在达到一定干预剂量(如0.2g/kg)后能有效控制其对小鼠的毒性,基本无毒效反应；能抑制人结肠癌HCT116细胞裸鼠原位移植瘤的生长,其效果与伊立替康相似,可能具有潜在的临床抗结直肠癌作用。
[Abstract]:Objective: to study the relationship between the toxicity of Fujiangyangyangyangyangyangyangyue and hMLH1 deletion of mismatch repair gene in colorectal cancer. Methods: human colorectal cancer HCT116 cells expressing green fluorescent protein were used to establish nude mouse colon cancer model by surgical operation in aseptic environment. Tumor bearing mice successfully transplanted with HCTll6 cells were randomly divided into 6 groups with 8 mice in each group. According to the results of LD50 in acute toxicity test, three kinds of yolk were divided into three groups: high, medium and low concentration as experimental group, normal saline as negative control group, and Iritekang as positive control group. The rats in the Fujinhuang group were given three doses of lianghuang once a day, and the positive control group were given 5-fluorouracil and irinotecan intraperitoneally, once every other day. Daily observation and recording of animal death, nutritional and activity status, adverse reactions, the use of animal in vivo fluorescence imaging system to measure tumor size at a fixed time point, and said weight. After 25 days of treatment, tumor vascular density, tumor size and metastasis were observed under fluorescence system. Results: after drug intervention, the mean mass and volume of tumor in the 0.2g/kg yolk group were significantly lower than those in the control group (0.52 卤0.24g vs 1.21 卤0.63g; 481.0 卤226.5mm3 vs 956.5 卤780.1mm3) (P0.05). The mean mass and volume of the tumor in the Ilitecam hydrochloride group were lower than those in the control group (0.28 卤0.13g vs 1.21 卤0.63g; 258.0 卤126.2mm3 vs 956.5 卤780.1mm3). The difference was statistically significant (P0.05). No statistical significance was found in the statistical results of the observation points or the end points of the experiment (P0.05). At the end of the experiment, pancreatic and lymph node metastases were observed in various groups of tumor-bearing mice under fluorescence system, and no drug-related adverse reactions were observed in each group (except for pre-experiment). The individual weight of tumor-bearing nude mice in each experimental group has not been significantly fluctuated. Conclusion: Fujinhuang can effectively control the toxicity of 0.2g/kg to mice and inhibit the growth of orthotopic transplantation of human colon cancer HCT116 cells in nude mice after reaching a certain intervention dose (such as 0.2g/kg), and its effect is similar to that of irinotecan. It may have a potential clinical anti-colorectal cancer effect.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R285

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