α7nACh受体竞争性拮抗剂甲基牛扁亭对昆明小鼠认知功能的损伤  

Mechanism of cognitive impairment by α7nAChR competitive antagonist methyllycaconitine in mouse

作　　者：苗珍花[1] 王银[1] 田建英[1] 丁玉梅[2] 

机构地区：[1]宁夏医科大学人体解剖学与组织学胚胎学系,银川750014 [2]宁夏医科大学附属医院中医科,银川750014

出　　处：《解剖学杂志》2010年第6期764-767,共4页Chinese Journal of Anatomy

基　　金：国家自然基金（30960108）;宁夏回族自治区自然基金（NZ09103）

摘　　要：目的：探讨α7nAChR竞争性拮抗剂甲基牛扁亭（MLA）对昆明小鼠认知功能的损伤.方法：给予昆明小鼠腹腔注射MLA高、中、低剂量（1 0、 2.4、 4 8μg·g-1） 1、 3、 6d后,观察各实验组小鼠学习行为、脑细胞超微结构改变以及脑细胞α7nAChR免疫组织化学阳性表达的变化.结果：在定位航行实验和空间探索实验中,MLA 1d高、中、低剂量组和3d、 6d中、低剂量组小鼠的逃逸潜伏期、在目标象限的时间分布与对照组比较均无统计学意义,而MLA 3d和6d高剂量组小鼠的逃逸潜伏期较对照组明显延长,其在目标象限的时间分布也较对照组明显减少; 6d高剂量组海马、皮质区神经细胞超微结构损伤比较严重;MLA 3d、 6d高剂量组小鼠脑海马、皮质区α7nAChR阳性表达与对照组比较明显增多.结论：实验小鼠腹腔连续注射MLA 4.8μg·g-1 3d、 6d能够造成实验小鼠学习记忆损伤,其机制可能是通过对脑海马和皮质区神经元超微结构的损伤而实现.Objective： To investigate the mechanism of cognitive impairment by a7nAChR competitive antagonist methyllyca-conitine （MLA） in mouse. Methods： Experimental mice were injected intraperitoneally with MLA （1.0, 2. 4, 4. 8 μg·g-1 ） or its saline vehicle, for 1, 3 or 6 days. and then learning and memory function were evaluated by Morris water maze. The ultrastucture of the cortex neurons and hippocampus neurons were observed; and the expression level of α7nAChR in cortex neurons and hippocampus neurons was detected by immunohistochemistry. Results： In place navigation tests, groups of trea- ting with MLA 4. 8 μg·g-1 for 3 d and 6 d were progressively longer than the control groups, the other groups were not progressively longer than the control groups in spatial probe tests, the average percentages of the swimming time in target quadrant were also decreased than the control groups, the other groups were also not decreased than the control groups; the ultrastructures of the cortex neurons and hippocampus neurons： the morphology in groups of treating with MLA 4. 8 μg·g-1 for 3 d and 6 d were not better preserved than the control group. The other groups were as same as the control group; the expression level of α7nAChR in cortex neurons and hippocampus neurons： the numbers of a7nAChR positive ceils in groups of treating with MLA 4. 8μg·g-1 for 3 d and 6 d were higher than the control groups, the other groups were not significant difference compared with the control group. Conclusion： These results suggest that MLA 4. 8 μg·g-1 can cause cognitive impairment of mouse, the mechanism may be ultrastructure damage of the cortex neurons and hippocampus neurons.

关 键 词：甲基牛扁亭 α7型神经烟碱胆碱能受体 超微结构 认知 小鼠 

分 类 号：R966[医药卫生—药理学]