Cuprizone诱导脱髓鞘模型各阶段的病理学和行为学研究.docVIP

Cuprizone诱导的脱髓鞘模型病理学和行为学研究 黄嘉璐1，陈康宁1，白莲花2，穆建坤3，孟召友1，周振华1（400038重庆，第三军医大学西南医院：神经内科1，肝胆外科2，康复科3） [摘要] 目的：探索Cuprizone诱导的脱髓鞘模型各个时间段的病理学及行为学变化规律，为相关临床研究提供参考。 方法：选取8周龄C57BL/6雄性小鼠，随机分为正常组和模型组，模型组又分急性脱髓鞘组与慢性脱髓鞘组。模型组小鼠饲养含有0.2% Cuprione的混合鼠粮，急性脱髓鞘组连续饲养6周，每周分别取材，慢性脱髓鞘组连续饲养Cuprizone鼠粮12周，12周末取材，正常组饲养正常鼠粮。实验过程中通过卢卡斯快蓝染色（Luxol fast blue, LFB）评估脑组织胼胝体区髓鞘脱失程度，利用免疫组化和Western blot技术检测胼胝体区髓鞘碱性蛋白（Myelin basic protein, MBP）和胶质纤维酸性蛋白（Glial fibrillary aidic protein, GFAP）的蛋白表达，最后结合行为学检测(旋转棒和旷场试验)探讨分析该模型的变化规律和特点。 结果：与正常组相比，LFB染色发现模型组小鼠胼胝体区髓鞘随着时间的延长逐渐脱失(P0.05)，MBP也验证此结果(P0.05)，通过对GFAP的检测发现星形胶质细胞随着时间的推移逐渐增多(P0.05)。旋转棒实验发现小鼠运动功能在第1周急剧下降，后保持在缓慢下降的水平(P0.01)；与正常组相比，急性脱髓鞘小鼠旷场试验结果与正常组无差别(P＞0.05)，慢性组有显著差别(P0.01)。结论：Cuprizone诱导的脱髓鞘小鼠模型随着时间的延长髓鞘逐渐脱失，星形胶质细胞逐渐增多，运动功能出现退化，这些变化之间存在相关联系。 关键词： Cuprizone；脱髓鞘；多发性硬化；星形胶质细胞；行为检测肝胆科 通信作者：陈康宁 E-mail：ckn_640827@126.com The pathological and behavioral characteristics of Cuprizone-induced demyelination model Huang Jialu1,Chen Kangning1,Bai Lianhua2, Mu Jiankun3, Meng Zhaoyou1, Zhou Zhenhua1 (1Department of Neurology, 2Department of Hepatology，3Department of Rehabilitation ,Southwest hospital, Third Military Medical University, ChongQing, 400038) [Abstract] To explore the pathological and behavioral characteristics in Cuprizone-induced demyelination mouse model at each stage and their relationship. Method: Eight- week old male C57BL/6 mice were used in this study which were divided into control group and experimental group randomly. The experimental group included acute demyelination model and chronic demyelination model. Acute demyelination model was fed with mixed diets containing 0.2% Cuprione for 6 weeks which was detected every week; chronic demyelination model was treated with cuprizone for 12 weeks which tissue was obtained at the end of the 12th week. Control group was fed normal diet everyday. The overall function was analysed by body weight. The Motor function was observed by rotarod test and open-field test. The degree of demyelination in cerebral callo