脑立体定位侧脑室注射海人酸构建癫痫大鼠模型的剂量探讨  

Study on the best dosage of kainic acid injected into the lateral ventricle of the brain in inducing rat model of epilepsy

作　　者：郭振宇[1] 胡蝶 黄凤[2] 杨璐平 盖聪[1] 冯琬迪 冯婧[1] 韩梅[1] 孙红梅[1] Guo Zhenyu;Hu Die;Huang Feng;Yang Luping;Gai Cong;Feng Wandi;Feng Jing;Han Mei;Sun Hongmei(Department of Human Anatomy,Bejing University of Chinese Medicine,Bejin 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]首都医科大学附属北京中医医院

出　　处：《脑与神经疾病杂志》2022年第7期397-402,共6页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金青年科学基金项目(No.81803857);北京中医药大学实验技术标准化研究项目(2015-JYB-JSMS018)。

摘　　要：目的 通过比较脑立体定位侧脑室注射不同剂量海人酸(KA)致痫效果探索大鼠癫痫模型的最佳注射剂量,为癫痫临床新药开发、日常用药指导及其发病机制的研究提供更理想的癫痫模型工具。方法 118只Wistar大鼠,按随机数字表法分为正常组20只、KA0.5μg组20只、KA 1μg组20只、KA1.5μg组28只和KA2μg组30只,采用脑立体定位侧脑室注射KA复制癫痫模型后,观察各组大鼠的Racine分级和动物死亡率比较癫痫大鼠的造模成功率,水迷宫实验检测大鼠的学习记忆能力,并通过苏木精-伊红染色、Nissle染色和免疫组化技术观察各组大鼠脑内损伤海马区的病理改变。结果①与正常组比较,注射不同剂量KA模型组均可导致不同程度的脑损伤,KA 1μg剂量组的造模成功率高于其他各组(P<0.005)。水迷宫实验在定位航行实验中,1μg以上的各剂量组和正常组比较,第4、5天逃避潜伏期出现明显的延长(P<0.05),在空间探索实验中,1μg以上的各剂量组和正常组比较,穿越原平台位置次数明显减少(P<0.05);②与正常组比较,1μg以上的各剂量组大鼠海马区神经元均出现明显损伤(P<0.05),大鼠海马区MAP2阳性细胞数降低(P<0.05)。结论 KA 1μg以上的各剂量组相比正常组海马区均有不同程度的损伤,但从大鼠的造模成功率相比,注射1μg比其他组有较大优势,所以将癫痫模型脑内注射KA的最佳剂量选定为1μg,为癫痫动物模型的制备提供参考依据。Objective To explore the best injection dose in inducing rat epilepsy model by comparing the effects of different doses of kainic acid(KA) injected into the lateral ventricle of the brain and to provide a more ideal tool for epilepsy clinical new drug development,daily medication guidance and related mechanism researchs.Methods118 Wistar rats were randomly divided into 5 groups,20 in the normal group,20 in the KA0.5 μ g group,20 in the KA1 μg group,28 in the KA 1.5 μg group and 30 in the KA 2 μg group.The epilepsy model was induced by stereotactic brain injection of KA into the lateral ventricle.① By observing the Racine classification and animal mortality of each group of rats,the success rate in inducing epileptic rats was compared,and the learning and memory ability of rats was tested by water maze experiment;② The pathological changes of the injured hippocampus in the brain of each group of rats were observed by HE staining,Nissle staining and immunohistochemistry.Results ① Compared with the normal group,the injection of different doses of KA model group can cause different degrees of brain damage.The success rate in the KA 1 μg dose group is higher than that in other groups(P<0.005).In the water maze experiment,compared with the normal group,the escape latency of each dose group above 1 μg was significantly prolonged on the 4 th and 5 th day(P<0.05).In the space exploration experiment,each dose above 1 μg,compared with the normal group,the number of crossing the original platform position was significantly reduced(P<0.05);② Compared with the normal group,the neurons in the hippocampus of rats in each dose group above 1 μg were significantly damaged(P<0.05),and the number of MAP2 positive cells in the hippocampus of rats decreased(P<0.05).Conclusion Each dose group with KA1 μg or more could cause different degrees of damage to the hippocampus compared to the normal group.However,compared with the success rate,injection of 1 μg has a greater advantage than the other groups,so the optimal dose

关 键 词：海人酸 癫痫模型 脑立体定位 最佳剂量 

分 类 号：R742.1[医药卫生—神经病学与精神病学]