脑膜癌病小鼠模型实验方法的改进  

A modified mouse model of leptomeningeal carcinomatosis

作　　者：李媛媛[1] 刘亚坤[1] 李忠尧[1] 韩玮欣 何俊瑛[1] 卜晖[1] LI Yuanyuan;LIU Yakun;LI Zhongyao;HAN Weixin;HE Junying;BU Hui(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《中国神经精神疾病杂志》2018年第8期471-475,共5页Chinese Journal of Nervous and Mental Diseases

摘　　要：目的对脑膜癌病(leptomeningeal carcinomatosis,LC)动物模型的实验方法进行改进,建立操作简单、重复性较好的脑膜癌病小鼠模型。方法雌性C57BL/6小鼠35只,20只随机分为对照组和实验组,每组10只,分别经小脑延髓池(cisterna magna,CM)穿刺注射无菌磷酸盐缓冲液(phosphate buffered saline,PBS)或Lewis肺癌细胞(lewis lung carcinoma cell,LLC)悬液7.5μL(1.5×105个细胞),观察评估注射后两组小鼠体质量随时间变化及神经系统症状表现;15只随机分为正常对照组(n=3)、PBS组(n=6)和模型组(n=6),当小鼠症状表现明显时,HE染色观察软脑(脊)膜病理改变。结果 小脑延髓池注射PBS或LLC细胞悬液后第11天开始,对照组小鼠体质量逐渐增加,而实验组小鼠体质量进行性下降直至死亡,差异有统计学意义[第11、13、17、21、25、29、33、37天,两组小鼠体质量分别为(18.84±1.66)g,(17.01±1.79)g;(17.21±1.49)g,(15.56±1.37)g;(17.73±1.51)g,(14.34±1.16)g;(18.37±1.38)g,(13.33±1.26)g;(18.84±1.66)g,(13.10±0.78)g;(18.83±1.84)g,(12.14±0.87)g;(19.73±1.90)g,(11.39±0.93)g;(20.25±1.92)g,(10.33±0.71)g,t依次为-2.378,-2.583,-5.636,-8.283,-8.462,-9.798,-8.258,-6.981,均P<0.05]。实验组小鼠均在40 d内死亡,中位生存时间为32.5d,对照组小鼠均至观察终点40 d仍存活,差异有统计学意义(P<0.05)。实验组小鼠小脑延髓池注射LLC细胞后症状出现在第10~16天,平均为(13±2)d;对照组小鼠均活动正常。HE染色显示模型组小鼠脑与脊髓软膜组织可见肿瘤细胞浸润,以脑基底部及脊髓颈段多见。结论 小脑延髓池注射Lewis肺癌细胞可成功建立肺癌来源脑膜癌病小鼠模型。Objective To develop an easy and reproducible mouse model of leptomeningeal carcinomatosis via Cisterna magna(CM)injection of Lung carcinoma cells.Methods Twenty female C57BL/6 mice were divided into two groups randomly and injected with either CM injection of PBS or cell suspension of Lewis Lung carcinoma cells(1.5×105 cells)7.5μL,respectively.The body weights and the neurological manifestations were assessed following CM injection.In addition,another 15 mice were divided into three groups including control(n=3),PBS(n=6)and LLC(n=6).When mice had obvious symptoms,they were sacrificed and the tissue sections of brain and spinal cord were stained by using hematoxylin-eosin staining.Results On the day 11,mice in LLC group exhibited progressive weight loss till death,while mice in control group still slowly gained the body weights still increased(P<0.05).All animals in LLC model group(n=10)died within 40 days and the median survival time was 32.5 d.In contrast,all animals(n=10)in the PBS group survived till endpoint(P<0.05).LLC-injected mice developed symptoms starting from day 10 to day 16 with an average of(13±2)d.HE staining showed a diffuse infiltration of malignant tumor cells into the leptomeninges and subarachnoid space in mice with LLC injection.Tumor cells were mainly located in the base of the brain and the cervical cordConclusion It is feasible to develop a mouse model for leptomeningeal carcinomatosis via CM injection of Lewis lung carcinoma cells injection.

关 键 词：脑膜癌病 小脑延髓池 LEWIS肺癌 

分 类 号：R651[医药卫生—外科学]