慢性脑低灌注对2型糖尿病模型大鼠空间学习记忆能力的影响及胆碱能神经元损伤的机制探讨  

Aggravation of Spatial Learning and Memory Impairment by Type 2 Diabetes in Rats with Chronic Cerebral Hypoperfusion is Associated with Cholinergic Neuron Injury

作　　者：李玉梅[1] 张婷[1] 肖品品[1] 张潇 付剑亮[1] 

机构地区：[1]上海交通大学附属上海市第六人民医院神经内科,200233 [2]中国科学院上海生命科学研究院,200031

出　　处：《中国临床神经科学》2013年第6期614-619,共6页Chinese Journal of Clinical Neurosciences

基　　金：上海市医学会"神经疾病转化研究"科学基金资助课题(编号:SHNR-006)

摘　　要：目的探讨2型糖尿病（DM）是否加重慢性脑低灌注（CCH）大鼠胆碱能神经元及空间学习记忆能力损伤。方法SD大鼠24只，随机分为4组（均n=6）：①对照组（正常饮食＋假手术）；②DM组[高脂饮食＋链脲佐菌素（STZ）]；③CCH组[正常饮食＋双侧颈总动脉永久性结扎（2-VO）]；④DM-CCH组（高脂饮食＋STZ＋2-VO）。采用Morris水迷宫测试各组大鼠学习记忆能力；免疫组化学法检测海马区乙酰胆碱转移酶（CHAT）阳性细胞表达和免疫印迹法检测海马ChAT相对表达量。结果DM＋CCH组逃避潜伏期与对照组比较明显延长，第2-4天（P〈0．001）、第5天（P〈0．01）；目标象限时『目】百分比明显低干对照组（P〈0．01）、DM组（P〈0．05）和CCH组（尸〈O．05）。DM＋CCH组海马区ChAT阳性细胞表达明显减少，ChAT相对表达量较对照组显著减少（P〈0．01）、DM组（P〈0．05）和CCH组（P〈0．05）显著减少。结论DM可加重CCH大鼠的空间学习记忆能力障碍，可能与海马区胆碱能神经元损伤有关。Aim To explore whether type 2 diabetes elicits cholinergic neuron injury, spatial learning and memory impairment in rats with chronic cerebral hypoperfusion. Methods 24 SD rats were randomly divided into 4 groups （n=6 in each group）： ① Control group （normal diet ＋ sham）; ② DM group （high-fat diet＋STZ injection）; ③CCH group （normal diet＋2-VO）; ④DM ＋ CCH group （high-fat diet＋STZ injection＋2-VO）. All rats were submitted to behavioral testing for spatial memory in Morris water maze. Immunohistochemical staining was used to detect hippocampal ChAT positive cells expression. The relative expression of ChAT in hippocampus were detected with Western blotting. Results Escape latency of DM＋CCH group was significantly longer than other groups （from the 2nd to 4th day, P〈0.001; at day 6, P〈0.01）; the percentageof time in the target quadrant was significantly reduced compared with the control group （P〈0.01 ）, CCH group （P〈0.05） and DM group（P〈0.05）. Compared with other groups, ChAT-positive cells significantly reduced in the hippocampus of DM＋CCH group. The relative expression of ChAT in the hippocampus of the DM＋CCH group decreased statistically, compared with the control group（P〈0.01L DM group（P〈0.05） and CCH group （P〈0.05）. Conclusion Diabetics exacerbates spatial learning and memory impairment in rats with chronic cerebral hypoperfusion, which may be related to hippocampal cholinergic neuron injury.

关 键 词：糖尿病 慢性脑低灌注 认知功能障碍 乙酰胆碱转移酶 胆碱能神经元 空间学习记忆 

分 类 号：R743[医药卫生—神经病学与精神病学]