CART肽抑制NMDA诱导海马神经元凋亡的机制  

Inhibitory effect of CART on apoptosis induced by NMDA in hippocampal neurons

作　　者：吴彬[1,2] 胡胜娣[1] 邱彬[1] 黄磊[1] 潘慧[1] 祝世功[1] 

机构地区：[1]北京大学医学部生理学与病理生理学系,北京100191 [2]北京市药品监督管理局

出　　处：《中国病理生理杂志》2009年第7期1325-1330,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30770804;No.30871034)

摘　　要：目的:探讨可卡因-苯丙胺调节转录肽(CART)对兴奋性氨基酸N-甲基-D-天冬氨酸(NM-DA)诱导海马神经元凋亡的作用和机制。方法:18dSD大鼠胚胎(E18)海马神经元原代培养8d,用MTT吸光度值、DNA ladder、Hoechst染色、Western blotting方法观察NMDA引起的神经元凋亡,以及CART肽对NMDA诱导的细胞凋亡的影响,分析CART肽的作用机制。结果:CART肽预处理组海马神经元存活率明显高于NMDA组(P<0.05);DNA ladder和核形态Hoechst染色证明,CART肽明显抑制NMDA诱导的海马神经元凋亡(P<0.01)。CART肽预处理明显促进NMDA组海马神经元中Bcl-2表达(P<0.01),增加Bcl-2/Bax比值,抑制caspase-9及caspase-3活化(P<0.01);但CART肽对Bax的表达及caspase-8活化无显著影响。结论:CART肽抑制NM-DA诱导的海马神经元凋亡,呈明显的神经保护作用,其神经保护机制主要是提高抗凋亡分子Bcl-2表达,抑制线粒体凋亡途径启动分子caspase-9和执行分子caspase-3的活化。AIM ： To study the role and mechanisms of cocaine - and amphetamine - regulated transcript peptide （CART） on NMDA induced apoptosis in primary cultured hippocampal neurons. METHODS： The primary cultured hippocampal neurons were established from embryonic rats （day 18 of gestation）. Cell viability was determined by MTT assay. DNA ladder and Hoechst staining were used to observe apoptosis in hippocampal neurons. Protein expression was examined by Western blotting. RESULTS： MTT assay indicated that CART enhanced neuronal viability. CART sustained neurons survival and protected neurons from NMDA - induced injury. Pretreatment with CART markedly increased the ex- pression of Bcl - 2 to the ratio of Bcl - 2 and Bax in hippocampal neurons in NMDA - injured group. CART also inhibited the activation of caspase-9 and caspase -3. However, CART did not affect the expression of Bax and the activation of caspase - 8 in normal hippocampal cultures. CONCLUSION ： CART provides neuroprotective effects on NMDA - induced apoptosis in cultured hippocampal neurons by increasing Bcl - 2 expression and inhibiting the activation of caspase - 9 and caspase - 3.

关 键 词：可卡因-苯丙胺调节转录肽 N-甲基-D-天冬氨酸 海马 神经元 半胱氨酸天冬氨酸蛋白 酶 蛋白质BCL-2 

分 类 号：R363[医药卫生—病理学]