吉西他滨时辰给药治疗荷瘤裸鼠的实验研究

【摘要】〓目的〓建立肺癌A549细胞裸鼠皮下注射成瘤模型,按照昼夜的不同时辰给予吉西他滨,观察其疗效和副作用,初步筛选出最佳给药时间。方法〓32只裸鼠饲养在SPF级实验动物房,统一光照条件,光照时间(7:30~19:30),黑暗时间(19:30~7:30),温度控制在25℃左右,湿度控制在50%左右;收集对数生长期培养的A549细胞,浓缩成2×107/mL的细胞悬液,在无菌条件下抽取约0.2 mL细胞悬液注射至裸鼠皮下。待肿瘤长到约1 cm×1 cm×1 cm大小,随机分为4组,每组8只。前三组按照时辰2 am、8 am、14 pm给予吉西他滨(50 mg/Kg),隔两天给药一次,持续三周,第四组给予等量无菌生理盐水作为对照组。每周测量肿瘤体积和裸鼠体重,绘制肿瘤的生长曲线和体重变化曲线。第30天处死裸鼠,抽血测肝肾功能,留取标本做HE染色观察镜下改变。结果〓吉西他滨对A549肺癌裸鼠移植瘤有治疗效果,其中2 am组抑瘤效果最明显,肿瘤生长最慢,裸鼠体重增长最快;8 am组抑瘤效果最差,肿瘤生长最快,裸鼠体重增长最慢。光镜下可见吉西他滨治疗组肺肝肾损伤较对照组减轻,肝肾功能改善(P<0.05,8 am、14 pm组vs.对照组;P<0.01,2 am组vs.对照组);药物治疗组当中,2 am组治疗效果最好,8 am组治疗效果最差(P<0.05,2 am vs. 8 am组)。结论〓吉西他滨对A549肺癌移植瘤裸鼠有明显的抑瘤作用,而且疗效和副作用呈时辰节律变化,2 am组疗效最佳,8 am组疗效最差。

Experiment study on gemcitabin echrono-chemotherapy to nude mice bearing the tumor

Objective To construct the model of nude mice bearing lung cancer A549 cell line. The curative effect and side effect were observed after gemcitabinechrono-chemotherapy, and the best time to administer drug was screened out. Methods A549 cells （2×10^7/mL） in exponential phase of growth were vaccinated in the nude mice by subcutaneous injection. Gemcitabine （50 mg/kg） was administrated by intraperitoneal injection at 2 am,8 am, 14 pm in experimental groups and equal sodium chloride in control group when the tumor growing to reach 1 cmxl cm~l cm approximately. The growth and weight curves were drawn by measuring data and blood and tissue specimen were hurvested. Results Gemcitabine had therapeutic effect on nude mice bearing tumor, in which the lesion of lung, liver and renal in the therapeutic groups was alleviated as compared with that in control group, and hepatorenal function was ameliorated in the administrated group. But there were differences among those groups on the therapeutic efficacy, the 2 am group showed the best effect while the 8 am group had the worst effect（P〈0.05, 8 am, 14 pm, 20 pm group vs. hepatoma model group; P〈0.01, 2 am group vs. hepatomamodel group; P〈0.05, 2 am group vs. 8 am group）. Conclusion Gemcitabine has therapeutic effect on nude mice bearing tumor, which can retain the growth of tumor, may alleviate the lesion of lung, liver and renal, ameliorate hepatorenal function caused by tumor as well. There were different curative effects in accordance with different administration time. There was the best therapeutic effect in the 2 am group while there was the worst effect in 8 am group.