丁苯酞对血管性痴呆大鼠记忆功能及海马神经元代谢产物的影响  

Effect of butylphthalide on memory function and hippocampal neuronal metabolites in vascular dementia rats

作　　者：孙晓鸣[1] 鲍君杰[1] 张华[1] 赵合庆[2] 张彩元[3] 朱莉萍[4] 

机构地区：[1]苏州大学附属第二医院药剂科,江苏苏州215000 [2]苏州大学附属第二医院神经内科,江苏苏州215000 [3]苏州大学附属第二医院磁共振室,江苏苏州215000 [4]华中科技大学基础医学系,湖北武汉430000

出　　处：《中国生化药物杂志》2015年第2期84-87,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：2009博士点基金(20090142120015)

摘　　要：目的 探究丁苯酞（3-N-butylphthalide,NBP）对血管性痴呆（vascular dementia,VD）大鼠学习记忆功能及海马神经元代谢产物的影响.方法 90只健康雄性SD大鼠,随机选取10只为假手术组,其余80只用2VO法制作大鼠VD模型.术后8周共存活48只大鼠,随机分为VD模型组、NBP低剂量组、NBP中剂量组、NBP高剂量组4组,每组各12只.术后8周NBP低、中和高剂量组大鼠分别腹腔注射NBP12.5、25和50 mg/（kg＆#183;d）,VD模型组和假手术组则注射相同体积的0.5％ Tween-80溶液,所有大鼠均连续注射4周.采用定位航行试验和空间探索试验考察各组大鼠行为学变化,1 H-MRS法检测神经元代谢产物变化.结果 定位航行试验结果表明大鼠的学习记忆能力与DBP剂量成正比,即1～5 d,NBP中、高剂量组的平均逃离潜伏期低于模型组,差异均有统计学意义（P＜0.05）,空间探索试验结果表明DBP高剂量组能够显著改善大鼠学习记忆能力;1H-MRS检测结果表明与给药后VD模型组相比,NBP中、高剂量组NAA/Cr、Cho/Cr和mI/Cr与模型组之间的差异均有统计学意义（P＜0.05）,表明中、高剂量NBP对海马内神经胶质细胞的增生有明显促进作用,而NBP低剂量组则无明显作用.结论 丁苯酞可以对血管性痴呆模型大鼠的学习记能力起到改善作用,通过调节海马神经元代谢产物,达到改善VD作用.Objective To explore the hippocampal metabolic changes of butylphthalide intervened vasculardementia（ VD） rats and the functions of butylphthalide on learning and memory improvement. Methods 10 rats were randomly selected from 90 healthy male SD rats to be sham operation group,and the remaining 80 rats were given 2VO surgery to make VD models. 48 rats survived after 8 weeks,and then randomly divided into 4 groups：VD model group,NBP low,medium,high dose group,each had 12 rats. Rats of NBP low,medium,high dose group were injected NBP 12. 5,25,50 mg /（ kg·d）,respectively. VD model group and sham operation group were injected with the same volume of 0. 5% Tween-80 solution,all rats were continuous injection of 4 weeks. Behavior test was investigated by place navigation test and spatial probe test. Changes of neuronal metabolites were detected by1H-MRS. Results Behavior test results indicated that rats＇ learning and memory ability were proportional to the DBP dose： 1 ~ 5 days,the average escape latency in NBP medium,high dose group were significantly lower than model group（ P〈 0. 05）,and spatial probe test results indicated that DBP high dose group could significantly improve the learning ability of rats;1H-MRS detection results showed that compared with after administration of VD with those in the model group,NAA / Cr,Cho / Cr and m I / Cr in medium dose group and high dose group,the differences were statistical significance（ P〈 0. 05）,but no statistical significance in NBP low dose group. The results indicated that the middle dose group and high dose group of glial cells in hippocampus hyperplasia had obvious effect,and low dose NBP group had no obvious effect. Conclusion Butylphthalide can improve the ability of learning and memory in rats with vascular dementia,and regulate hippocampal neuronal metabolites to improve function of VD.

关 键 词：丁苯酞 血管性痴呆 水迷宫 海马神经元代谢 

分 类 号：R74[医药卫生—神经病学与精神病学]