阿魏酸钠对慢性脑低灌注大鼠认知功能及对磷酸化ERK、CREB和BDNF表达的影响

Effect of Sodium Ferulate on Cognitive Improvement and Expression of p-ERK,p-CREB,and BDNF in Chronic Cerebral Hypoperfusion Rats

目的:观察阿魏酸钠对慢性脑低灌注大鼠空间学习记忆能力及对海马细胞外信号调节激酶(ERK 1/2)、环磷酸腺苷反应元件结合蛋白(CREB)的磷酸化(p-ERK及p-CREB)和脑源性神经营养因子(BDNF)表达的影响。方法:将SD大鼠随机分为3组,假手术组(SHAM+NS)、慢性脑低灌注组(2VO+NS)、阿魏酸钠治疗组(2VO+SF)。采用新奇物体识别试验、Morris水迷宫检测3组大鼠的认知;用Western Blot检测3组大鼠海马中的p-ERK、p-CREB、BDNF的表达。结果:通过行为学检测,模型组大鼠识别新物体能力下降,阿魏酸钠可以缓解这种下降趋势(P<0.05)。模型组大鼠Morris水迷宫中逃避潜伏期延长,空间探索时间明显减少;阿魏酸钠治疗组可以缩短大鼠的逃避潜伏期(P<0.05),空间探索时间明显增加(P<0.05)。模型组p-ERK、p-CREB、BDNF的表达较假手术组明显下降(P<0.05,P<0.01,P<0.001),治疗组p-ERK、BDNF的表达较模型组显著升高(P<0.01,P<0.05)。结论:阿魏酸钠能改善慢性脑低灌注大鼠空间学习记忆能力,其作用机制可能与介导了海马中p-ERK、p-CREB、BDNF的表达水平升高有关。

Objective：To observe whether the sodium ferulate can influence cognitive improvement in rats with chronic cerebral hypoperfusion,and the expression of p-ERK1/2,p-CREB,and BDNF in brain.Methods：All the rats were randomly divided into sham-operated（SHAM＋NS）group,bilateral common carotid artery ligation（2VO＋NS）group and sodium ferulate treatment（2VO＋SF）group.Object recognition test and Morris water maze were used to detect the cognition,and Western-blot was used to test the levels of p-ERK 1/2,P-CREB,and BDNF expression.Results：The ability of 2VO＋NS rats to identify new objects was decreased,while sodium ferulate could mitigate this decline（P〈0.05）.The escape latencies of 2VO＋NS rats were extended and spatial probe time of 2VO＋NS rats was decreased,while sodium ferulate could shorten the escape latencies significantly（P〈0.05）and increase the spatial probe time（P〈0.05）.Compared with thesham group,the expression of p-ERK 1/2,p-CREB and BDNF in 2VO＋NS group significantly decreased（P〈0.05,P〈0.01,P0.001）,the expressions of p-ERK 1/2,p-CREB and BDNF in2VO＋SF group significantly increased（P〈0.01,P〈0.05）.Conclusion：Sodium ferulate can improve the cognition in rats with chronic cerebral hypoperfusion.Its mechanism may be mediated with a upregulation of ERK1/2and CREB phosphorylation,and BDNF expression.