新生期母婴分离对成年小鼠肿瘤生长的影响  

Impact of neonatal maternal separation on tumor growth in adult mice

作　　者：王晴[1] 蒙姿宏 宋艳芳[1] 胡晶莹[1] 姚明[1] 屠红[1] 甘愉[1] 

机构地区：[1]上海交通大学医学院附属仁济医院上海市肿瘤研究所癌基因及相关基因国家重点实验室,上海200032

出　　处：《肿瘤》2016年第3期245-253,共9页Tumor

基　　金：国家自然科学基金资助项目(编号:81101823;81571618);癌基因及相关基因国家重点实验室自主资助项目(编号:YYJJ-2014-02)~~

摘　　要：目的 :探讨新生期母婴分离(maternal separation,MS)作为一种生命早期应激对成年小鼠肿瘤生长的影响。方法 :C57BL/6小鼠在出生后3周内,每天和母鼠分开饲养6 h,建立小鼠MS模型。待小鼠6周龄(出生后第43天)时,用高架十字迷宫(elevated plus maze,EPM)行为学实验检测MS对小鼠焦虑水平的影响,并于出生后第45天时皮下接种胰腺癌Panc-02细胞,建立小鼠胰腺癌移植瘤模型,观察小鼠胰腺癌移植瘤的生长状况。结果 :新生期MS能明显降低雄性小鼠成年后在EPM开放臂中的活动时间(P<0.01)和活动路程百分比(P<0.05),并延长其进入开放臂的等待时间(P<0.01),提示MS提高了雄性小鼠成年后的焦虑水平。同时,MS能明显促进胰腺癌Panc-02细胞皮下移植瘤的生长(P<0.01)。胰腺癌Panc-02细胞接种小鼠35 d后,雄性MS组小鼠的移植瘤质量较正常对照组小鼠增加了56.8%,差异有明显的统计学意义(P<0.05)。然而,MS对雌性小鼠成年后的焦虑水平及胰腺癌移植瘤的生长均无明显影响(P值均>0.05)。结论 :生命早期母婴分离具有促进成年小鼠肿瘤生长的作用,且该作用可能存在性别差异。Objective：To investigate the influence of neonatal maternal separation（MS） on tumor growth in adult mice.Methods：C57BL/6 mice underwent a MS protocol whereby they were separated from their dams for 6 h in postnatal weeks 1-3.In early adulthood,6-week-old mice（43rd day after birth） were subjected to elevated plus maze（EPM） test,which was one of the most commonly used behavioral assays,in order to evaluate the influence of MS on the anxiety level of adult mice.Subsequently,the mice 45 days after birth were transplanted with Panc-02 cells to establish murine xenograft model of pancreatic cancer.The growth of xenograft tumors of adult mice undergoing MS was then observed.Results：Neonatal MS significantly decreased the time（P 〈 0.01） and the percentage of distance（P 〈 0.05） travelled in the open arms of EPM in male mice.Meanwhile,MS significantly increased the latency in open arms of EPM in male adult mice（P 〈 0.01）.These results suggested that MS in early life elevated the level of anxiety in male adult mice.Furthermore,MS in early life significantly promoted the growth of pancreatic cancer xenografts in adult male mice（P 〈 0.01）.At the time of 35 days after tumor transplantation,the tumor weight of male mice subjected to MS was ascended by 56.8%as compared with that of the control mice（P 〈0.05）.However,neonatal MS had no influence on the level of anxiety（P 〉 0.05） and the growth of pancreatic cancer xenografts（P 〉 0.05） in adult female mice.Conclusion：Maternal separation in early life confers a significant,but possibly genderdependent,promotory effect on cancer growth in adulthood.

关 键 词：胰腺肿瘤 母婴分离 应激 心理学 动物实验 

分 类 号：R735.9[医药卫生—肿瘤]