丁基苯酞对慢性脑缺血大鼠脑保护机制的研究

目的观察丁基苯酞(NBP)对慢性脑缺血老龄大鼠海马学习记忆及p-CREB和脑源性神经细胞生长因子(BDNF)表达的影响。方法选取健康Wistar大鼠80只,随机分为4组:对照组(A组)、单纯缺血组(B组)、缺血低剂量治疗组(C组)、缺血高剂量治疗组(D组)。每组20只。采用双侧颈总动脉结扎法(2VO)。各组大鼠于2VO前、2VO后2、3个月行Morris水迷宫试验进行学习记忆能力的评价,采用免疫组织化学法观察2VO后3个月NBP对大鼠海马中p-CREB及BDNF表达的影响。结果与A组比较,2VO后2个月B、C、D组大鼠逃避潜伏时间明显延长,跨过平台次数明显减少;与B组比较,2VO后3个月C、D组差异有统计学意义(P<0.05),D组与C组比较,均有所改善,差异有统计学意义(P<0.05,表1)。与A组比较,B组海马p-CREB及BDNF表达明显减少。与B组比较,C组、D组p-CREB和BDNF表达明显增加,差异有统计学意义(P<0.05)。结论 NBP能改善缺血,增加p-CREB及BDNF的表达。

Mechanism of protective effect of dl-butylphthalide on rat brain after chronic cerebral ischemia

Objective To observe the effect of dl-butylphthalide on learning,memory,expression of p-CREB and BDNF in hippocampus of aged rats after chronic cerebral ischemia.Methods Eighty healthy Wistar rats were selected and divided randomly in to 4 groups of 20 rats each:group A: control group(sham operation);group B:ischemia group;group C:ischemia and low dose treat- ment group;group D:ischemia and high dose treatment group.Chronic cerebral ischemia rat model was established by permanent occlusion and snip of bilateral common carotid arteries(2VO).Cog- nitive ability of all rats was evaluated by Morris water maze test before 2VO,two months and three months after 2VO.Three months after the operation,immunohistocbemical technique was used to observe the effect of dl-butylphthalide on p-CREB and BDNF in hippocampus.Results Compared with the control group,the expression of p-CREB and BDNF in the CA1,CA3 and DG of hippocampus were markedly decreased in the ischemia group.The expression of p-CREB and BDNF in hippocampus of rats in groups C and D were markedly increased as compared with the ischemia group.Compared with group C,the expression of p-CREB and BDNF was markedly in- creased in group D.Conclusion Dl-butylphthalide can improve cerebral ischemia and increase the expression of p-CREB and BDNF.