【摘要】 目的探究乳腺癌化疗常用药物紫杉醇、表柔比星、环磷酰胺对小鼠认知功能的影响。方法本研究运用随机数字表法将Balb/c小鼠分为4组,每组20只,实验组小鼠分别腹腔注射紫杉醇(30 mg/kg)、表柔比星(10 mg/kg)、环磷酰胺(200 mg/kg),对照组小鼠给予注射等体积的0.9%Na Cl溶液。给药4周后进行Morris水迷宫定位航行实验和空间探索实验,分别记录小鼠找到水下平台的时间(即逃避潜伏期),在目标象限时间占总时间的比率及穿越目标象限的次数。逃避潜伏期比较采用重复测量的方差分析,目标象限时间占总时间的比率比较采用单因素方差分析,穿越平台次数比较用Kruskal-Wallis秩和检验。结果在定位航行实验中,实验组和对照组小鼠在5个时间点(给药后第1、2、3、4、5天)的逃避潜伏期均随训练天数增加而逐渐缩短,呈下降趋势(F=11.25,P=0.001)。紫杉醇组、表柔比星组、环磷酰胺组与对照组小鼠逃避潜伏期差异无统计学意义,不同时间点差异有统计学意义(组间比较:F=1.23,P=0.251;时间点比较:F=5.94,P<0.001;组别与时间点的交互作用:F=0.77,P=0.676)。空间探索实验中,小鼠在目标象限的时间所占总时间的比率组间差异有统计学意义(F=3.26,P=0.027);与对照组相比,环磷酰胺组在目标象限的时间占总时间的比率降低(13.6%±8.9%比23.9%±13.9%,t=-3.05,P=0.009)。各组小鼠穿越平台次数差异无统计学意义(χ~2=1.86,P=0.602)。结论环磷酰胺可降低小鼠的空间记忆能力,部分化疗药有可能改变小鼠的空间学习记忆能力。更多还原

【Abstract】 Objective To explore the effects of paclitaxel,epirubicin and cyclophosphamide,which are widely used in breast cancer chemotherapy,on the cognition function of mice. Methods Totally 80 Balb / c mice were randomized into four groups,20 mice in each group. The mice in 3 experimental groups were intraperitoneally injected with paclitaxel( 30 mg / kg),epirubicin( 10 mg / kg),or cyclophosphamide alone( 200 mg/kg) respectively. The mice in control group were injected with isovolumic saline. At 4 weeks after injection,all groups were given Morris water maze test,including place navigation and spatial probe test,to record the time the mice spent on underwater platform( escape latency),the ratio of time in every quadrant to total swimming time and the times of crossing the platforma. The escape latencies of mice were compared among groups using repeated measurement analysis of variance,the ratio of time in every quadrant to total swimming time was compared using univariate analysis of variance and the times of crossing the platform among groups were compared using Kruskal-Wallis rank sum test. Results In place navigation test,the escape latencies at5 time points( on days 1,2,3,4,5 after injection) in four groups were decreased with training time,which showed a trend of decline( F = 11. 25,P = 0. 001). There was no statistically significant difference in escape latency between paclitaxel / epirubicin / cyclophosphamide-treated group and control group, while escape latencies were significantly different at 5 time points( comparison between groups: F = 1. 23,P = 0. 251;comparison at different time points: F = 5. 94,P < 0. 001; interaction between grouping and different time points: F = 0. 77,P = 0. 676). In spatial probe test,the ratio of time spent in every quadrant to the total swimming time in 4 groups presented a significant difference( F = 3. 26,P = 0. 027); it was significantly lower in cyclophosphamide-treated group than that in control group( 13. 6% ±8. 9% vs 23. 9% ±13. 9%; t =- 3. 05,P = 0. 009). The difference was not statistically significant between experimental groups and control group in the times of crossing the platform on the sixth day after injection( χ~2= 1. 86,P = 0. 602). Conclusions Cyclophosphamide can affect the memory maintenance of mice. There is a possibility that chemotherapy medication can affect the ability of spatial cognition and learning in mice.更多还原