小剂量环磷酰胺治愈荷膀胱癌小鼠动物模型的建立  

Experimental study on establishing mouse model of BTT739 tumor-bearing mice cured by a low dose of CTX

作　　者：李墨林[1] 姜妙娜[1] 舒晓宏[2] 崔晓栋[3] 李传刚[4] 贾玉杰[1] 

机构地区：[1]大连医科大学病理生理学教研室,辽宁大连116044 [2]大连医科大学药学院,辽宁大连116044 [3]潍坊医学院病理生理学教研室,山东潍坊261042 [4]大连医科大学附属第二医院泌尿外科,辽宁大连116027

出　　处：《大连医科大学学报》2008年第3期193-195,212,共4页Journal of Dalian Medical University

基　　金：辽宁省自然科学基金资助(20062156)

摘　　要：[目的]建立单一剂量环磷酰胺（cyclophosphamide,CTX）治愈荷膀胱癌小鼠的动物模型。[方法]T739小鼠皮下接种小鼠可移植性膀胱移行细胞癌组织建立荷瘤小鼠模型。肿瘤接种后第7天,不同剂量的CTX单次腹腔内注射,观察荷瘤小鼠用药后体重和肿瘤结节直径的变化,找出CTX可治愈多数荷瘤小鼠的最低有效剂量。然后再取12只荷瘤T739小鼠随机分成两组,最低有效剂量的CTX单次腹腔内注射,等量生理盐水作对照,分别在治疗后第4、14天内眦静脉取血进行白细胞计数。[结果]接种2 mm^3的小鼠膀胱癌肿瘤组织可使T739小鼠肿瘤进行性生长,接种后第7天肿瘤直径约为2-4 mm。15-400 mg/kg的CTX单次腹腔内注射后1周内,荷瘤小鼠肿瘤结节缩小的速率和毒性反应均与所用CTX的剂量呈正相关。CTX治疗后2月,100-200 mg/kg CTX治疗组的荷瘤小鼠全部死亡;40 mg/kg CTX治疗后20%的荷瘤小鼠存活;15 mg/kg CTX治疗组60%的荷瘤小鼠存活,与对照组比较差异具有统计学意义（P〈0.01）。15 mg/kg CTX治疗后第4天荷瘤小鼠外周血WBC为（11.36±0.30）×10^9/L,对照组为（11.14±2.14）×10^9/L,两组数据比较差异无统计学意义（P〉0.05）;治疗后第14天,治疗组小鼠WBC计数降为（8.46±0.76）×10^9/L,与CTX治疗后第4天WBC计数比较差异具有统计学意义（P〈0.05）,但与对照组（9.86±3.40）×10^9/L比较差异无统计学意义（P〉0.05）。[结论]15 mg/kg CTX单次腹腔内注射后荷瘤小鼠无明显毒性反应,并可使多数荷瘤小鼠肿瘤治愈,因此,小剂量CTX治愈荷膀胱癌小鼠模型成功建立。[ Objective] To establish an animal model of BTT739 mice cured by a single dose of cyclophosphamide （CTX）. [ Methods] Mouse bladder carcinoma tissue was inoculated subcutaneously into BTT739 mice. 7 days later, different doses of CTX were used intraperitoneally to treat these tumor - bearing mice. Tumor sizes and body weight were observed and recorded subsequently, and the minimal effective dose of CTX that could cure most of the tumor - bearing mice was found. Then another 12 tumor - bearing mice were randomly divided into two groups ： the minimal effective dose of CTX was given intraperitoneally and the same volume of NS as control. The WBC count was measured at the 4th and 14th days after treatment. [ Results] Inoculation of 2 mm^3 bladder carcinoma tissue could make tumor cell progressive growth in T739 mice. The tumor sizes were 2 -4 mm on day 7 after inoculation. Within 1 w after 15 - 400 mg/kg CTX treatment, the speed of tumor shrinkage and the side effects of tumor - bearing mice had a positive relationship with the dose of CTX used. 2 months after CTX treatment, no mice was alive in 100 -400 mg/kg CTX group; 20% of mice were alive in 40 mg/kg CTX group; 60% of mice were alive in 15 mg/kg CTX group. There was significantly difference between 15 mg/kg CTX group and control group （P 〈0.01 ）. On the 4th day after treatment, there was no significantly difference in peripheral blood WBC count in tumor - bearing mice between 15 mg/kg CTX group （ 11.36±0.30） × 10^9/L and control group （ 11.14±2.14） × 10^9/L （P 〉 0.05 ）. The WBC count decreased to （8.46±0. 76）×10^9/L in mice of CTX group on the 14th day after treatment. There was significantly difference in WBC count of the mice between the 4th and the 14th day after CTX treatment （ P 〈 0. 05 ） ; but there is no significantly difference compared with control group （9.86 ±3.40）×10^9/L （ P 〉 0. 05）. [ Conclusions] A single dose of CTX （15 mg/kg） had no obvious side effects, but could cure most of these tumor

关 键 词：环磷酰胺 小剂量化疗 动物模型 小鼠膀胱癌 T739小鼠 

分 类 号：R737.14[医药卫生—肿瘤] R-332[医药卫生—临床医学]