大剂量化疗动物模型的构建

发布时间：2019-04-19 01:47

【摘要】： 目的:利用SELDI技术构建大剂量化疗动物模型。方法:以成年雌性昆明小鼠为实验对象,通过右腋下接种肿瘤细胞悬液(0.2ml/只),建立小鼠S180肉瘤动物模型,随机分为三组,按动物用药标准,设定A组为常规化疗组(n=10):腹腔注射顺铂2.6mg/kg~*4天,B组为大剂量化疗组(n=10):腹腔注射顺铂5.2m g/kg~*4天,C组为超大剂量化疗组(n=10):腹腔注射顺铂5.2mg/kg~*7天,于用药结束后第三天给予小鼠摘眼球取血分离血清进SELDI检测,并利用Biomarker Wizard软件对不同用药剂量的血清进行蛋白质组指纹图谱的比较,找出差异蛋白质组。然后运用Biomarker Parrtern软件建立大剂量化疗动物模型的蛋白质指纹。结果:①常规化疗组和超大剂量化疗组:联合7个m/z位于3453,3869,4038,4219,4311,4903,5685的血清蛋白质指纹图谱模型用于区分常规化疗组和超大剂量化疗组,特异性为:77.778%(7/9),敏感性为88.889%(8/9),准确度为83.3%。 ②常规化疗组和大剂量化疗组:联合4个m/z位于4038,5685,2687,3869的血清蛋白质指纹图谱模型在区分常规化疗组和大剂量化疗组的特异性为77.778%(7/9),敏感性为:90%(9/10),准确度为84.3%。 ③大剂量化疗组和超大剂量化疗组:联合4个m/z位于2589,2870,6021,6980的血清蛋白质指纹图谱模型在区分大剂量化疗组和超大剂量化疗组的特异性为88.889%(8/9),敏感性为:90%(9/10),准确度为89.4%。 ④其中m/z位于5685,3869的血清蛋白质指纹图谱在超大剂量化疗、大剂量化疗与常规剂量组区分中被作为潜在的生物标记筛选了出来,它们在常规化疗组,大剂量化疗组和超大剂量化疗组中的表达依次升高其丰度分别是5685(3.55)(5.17)(6.26),3869(4.10)(8.79)(10.11):因此m/z位于5685丰度为5.17,3869丰度为8.79的蛋白质组指纹为肿瘤大剂量化疗相关指纹标识。结论:模型鼠血清经SELDI技术检测到m/z为5685丰度为5.17和3869丰度为8.79的蛋白质指纹视为建模成功。
[Abstract]:Objective: to establish the animal model of high dose chemotherapy by SELDI technique. Methods: the mouse model of S180 sarcoma was established by right axillary inoculation of tumor cell suspension (0.2ml/) in adult female Kunming mice. The mice were randomly divided into three groups according to the standard of animal drug use. Group A: routine chemotherapy group (n = 10): intraperitoneal injection of cisplatin for 2.6mg/kg~*4 days, group B for high-dose chemotherapy group (n = 10), intraperitoneal injection of cisplatin for 5.2m g/kg~*4 days, and intraperitoneal injection of cisplatin for 5.2m g/kg~*4 days. Group C: large dose chemotherapy group (n = 10): intraperitoneal injection of cisplatin for 5.2mg/kg~*7 days, the third day after the end of the drug was given to mice enucleated eyeball blood to separate the serum to be detected by SELDI. Biomarker Wizard software was used to compare the proteome fingerprints of serum with different dosages to find out the difference proteome. Then the protein fingerprints of high-dose chemotherapy animal model were established by Biomarker Parrtern software. Results: 1 routine chemotherapy group and ultra-high dose chemotherapy group: the serum protein fingerprint model was used to distinguish the conventional chemotherapy group and the super-dose chemotherapy group, the specificity was 77.778% (7 / 9), and the serum protein fingerprint model was located at 3453, 3869, 4038,4219,4311,4903,5685, respectively, in the conventional chemotherapy group and the super-dose chemotherapy group, with the specificity of 77.778% (7 / 9). The sensitivity was 88.889% (8 / 9) and the accuracy was 83.3%. (2) conventional chemotherapy group and high dose chemotherapy group: the specificity of the serum protein fingerprint model of 4038, 5685,2687,3869 in distinguishing conventional chemotherapy group and high dose chemotherapy group was 77.778% (7 / 9), combined with 4 mz in 4038, 5685,2687,3869 serum protein fingerprinting models, the specificity was 77.778% (7 / 9) in the conventional chemotherapy group and the high dose chemotherapy group. The sensitivity was 90% (9 脳 10) and the accuracy was 84.3%. (3) High-dose chemotherapy group and super-dose chemotherapy group: the specificity of the serum protein fingerprint model of the combination of 4 m-z at 2589, 2870, 6021, 6980 was 88.889% (8 / 9) in distinguishing the high-dose chemotherapy group and the super-dose chemotherapy group (P < 0.01), the specificity of the model was 88.889% (8 / 9) in distinguishing high-dose chemotherapy group from super-dose chemotherapy group. The sensitivity is 90% (9 / 10) and the accuracy is 89.4%. The serum protein fingerprints of 3869 were screened as potential biomarkers in the super-dose chemotherapy, high-dose chemotherapy and conventional chemotherapy groups, and they were screened as potential biomarkers in the conventional chemotherapy group, and the serum protein fingerprints of 3869 were identified as potential biomarkers at 5685,3869 were selected as potential biomarkers. The abundance of high-dose chemotherapy group and super-dose chemotherapy group were 5685 (3.55) (5.17) (6.26) and 5685 (3.55) (5.17) (6.26), respectively. 3869 (4.10) (8.79) (10.11): the proteome fingerprints with the abundance of 3869 (4.10) (8.79) (10.11) are therefore located at the abundance of 5685 to 5.17, and the proteome fingerprints with the abundance of 8.79 are the fingerprints associated with high-dose chemotherapy for tumors. Conclusion: the protein fingerprints with the abundance of 5685 to 5.17 and 3869 to 8.79 in the serum of the model mice detected by SELDI technique are considered as successful models.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R730.5;R-332

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