侧脑室注射PP2对慢性复合应激大鼠学习记忆功能和海马内Fyn、BDNF和TrkB表达的影响  

EFFECTS OF PP2 INJECTED INTO LATERAL VENTRICLE ON LEARNING AND MEMORY FUNCTION,EXPRESSION OF Fyn,BDNF AND TrkB IN THE HIPPOCAMPUS OF THE RAT BY CHRONIC MULTIPLE STRESS

作　　者：李晓恒[1] 刘能保[2] 张敏海[2] 廖家万[2] 周艳玲[2] 陈鸿伟[2] 刘向前[2] 

机构地区：[1]深圳市疾病预防控制中心,深圳518020 [2]华中科技大学同济医学院组织胚胎学教研室,武汉430030

出　　处：《神经解剖学杂志》2007年第5期530-535,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(No30270446)资助项目

摘　　要：为了探讨酪氨酸激酶抑制剂PP2对慢性复合应激性学习记忆增强大鼠的学习记忆功能和海马内非受体酪氨酸激酶(Fyn)、脑源性神经营养因子(BDNF)和Trk酪氨酸激酶B(TrkB)表达的影响,本实验将成年雄性大鼠22只,随机分为三组:即慢性复合应激组(对照组)、慢性复合应激+注射盐水组(盐水组)和慢性复合应激+注射PP2组(PP2组)。全部动物暴露于复合应激原中6周后,盐水组和PP2组动物分别侧脑室注射生理盐水或PP2(1次/d,共11d)。实验结束后,用Morris水迷宫测试大鼠的空间学习记忆成绩;采用免疫组织化学方法检测Fyn、BDNF和TrkB在海马内蛋白表达的变化。结果显示:与对照组和盐水组相比,PP2组动物的学习与记忆成绩明显下降(P<0.05);海马内Fyn和BDNF蛋白阳性表达减弱(P<0.05);但3组动物海马内TrkB的蛋白表达无显著性差异(P>0.05)。上述结果表明:侧脑室注射PP2可抑制大鼠慢性复合应激性学习记忆能力的增强作用,下调Fyn和BDNF在海马内的表达;提示Fyn和BDNF/TrkB信号转导途径在慢性复合应激增强大鼠学习记忆能力的过程中发挥重要作用。To investigate the effects of PP2, a tyrosine kinase inhibitor, on the function of learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of the rat whose leaning and memory was enhanced by chronic multiple stress, 22 adult rats were randomly divided into three groups ： chronic multiple stressed group （ control group）, chronic multiple stressed with injecting saline group （ saline group） and chronic multiple stressed with injecting PP2 group （PP2 group）. All rats were exposed to chronic multiple stress for 6 weeks, then rats of saline group and PP2 group were respectively injected saline or PP2 into the lateral ventricle（ 11 d with one time/d）. After that, the performance of spatial learning and memory of all rats was measured using Morris water maze. The expressional changes of Fyn, BDNF and TrkB proteins in the hippocampus of rats were detected by immunohistochemical method. The results showed that： compared with control group and saline group, the performance of spatial learning and memory of rats was decreased in PP2 group （ P 〈 0.05 ） ; the of Fyn and BDNF in the hippocampus were weakened in rats of PP2 group （ P 〈 0.05 ）, but no difference of TrkB protein expression in the hippocampus was observed in the three groups （ P 〉 0.05 ）. The above results indicate that PP2 injected into the lat-eral ventricle may degrade the function of rat＇s learning and memory, and downregnlate the expression of Fyn and BDNF in the hippocam- pus of the rat whose leaning and memory was enhanced by chronic multiple stress. It suggests that Fyn and BDNF/TrkB signal transductionpathway may play an important role in the process of the enhanced learning and memory by chronic multiple stress.

关 键 词：侧脑室注射 PP2 慢性复合应激 学习与记忆 酪氨酸激酶 脑源性神经营养因子 TRKB 海马 大鼠 

分 类 号：R363[医药卫生—病理学]