【摘要】： 目的:利用SELDI技術構建大劑量化療動物模型。 方法:以成年雌性昆明小鼠為實驗對象,通過右腋下接種腫瘤細胞懸液(0.2ml/只),建立小鼠S180肉瘤動物模型,隨機分為三組,按動物用藥標準,設定A組為常規(guī)化療組(n=10):腹腔注射順鉑2.6mg/kg~*4天,B組為大劑量化療組(n=10):腹腔注射順鉑5.2m g/kg~*4天,C組為超大劑量化療組(n=10):腹腔注射順鉑5.2mg/kg~*7天,于用藥結束后第三天給予小鼠摘眼球取血分離血清進SELDI檢測,并利用Biomarker Wizard軟件對不同用藥劑量的血清進行蛋白質組指紋圖譜的比較,找出差異蛋白質組。然后運用Biomarker Parrtern軟件建立大劑量化療動物模型的蛋白質指紋。 結果:①常規(guī)化療組和超大劑量化療組:聯(lián)合7個m/z位于3453,3869,4038,4219,4311,4903,5685的血清蛋白質指紋圖譜模型用于區(qū)分常規(guī)化療組和超大劑量化療組,特異性為:77.778%(7/9),敏感性為88.889%(8/9),準確度為83.3%。 ②常規(guī)化療組和大劑量化療組:聯(lián)合4個m/z位于4038,5685,2687,3869的血清蛋白質指紋圖譜模型在區(qū)分常規(guī)化療組和大劑量化療組的特異性為77.778%(7/9),敏感性為:90%(9/10),準確度為84.3%。 ③大劑量化療組和超大劑量化療組:聯(lián)合4個m/z位于2589,2870,6021,6980的血清蛋白質指紋圖譜模型在區(qū)分大劑量化療組和超大劑量化療組的特異性為88.889%(8/9),敏感性為:90%(9/10),準確度為89.4%。 ④其中m/z位于5685,3869的血清蛋白質指紋圖譜在超大劑量化療、大劑量化療與常規(guī)劑量組區(qū)分中被作為潛在的生物標記篩選了出來,它們在常規(guī)化療組,大劑量化療組和超大劑量化療組中的表達依次升高其豐度分別是5685(3.55)(5.17)(6.26),3869(4.10)(8.79)(10.11):因此m/z位于5685豐度為5.17,3869豐度為8.79的蛋白質組指紋為腫瘤大劑量化療相關指紋標識。 結論:模型鼠血清經(jīng)SELDI技術檢測到m/z為5685豐度為5.17和3869豐度為8.79的蛋白質指紋視為建模成功。
[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.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R730.5;R-332

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