中文摘要：

目的：探讨细胞外信号调节激酶（ERK）通路在可卡因-苯丙胺调节转录肽（CART）上调大鼠海马神经元脑源性神经营养因子（BDNF）表达中的作用。方法：取18 d的SD大鼠胚胎（E18）,分离海马神经元,体外原代培养7 d,以不同剂量CART处理细胞,用Western blotting方法分别检测不同处理时点p-ERK表达.再以ERK通路特异性阻断剂PD98059（25 μmol/L）预处理细胞,进一步观察CART对p-ERK表达及BDNF合成的影响。结果：同对照组比较,CART处理组海马神经元p-ERK表达明显增高（P＜0.01）,BDNF合成增加.PD98059能阻断内源性ERK磷酸化、也能阻断CART诱导的ERK磷酸化,同时抑制CRAT引起的BDNF合成。结论：CART通过激活ERK促进海马神经元BDNF的合成,从而发挥神经营养作用。

英文摘要：

AIM： To study the role of extracellular signal regulated kinase（ERK） pathway in cocaine -and amphetamineregulated transcript（CART） induced brain- derived neurotrophic factor （BDNF） synthesis in primary cultured hippocampal neurons. METHODS： The primary cultures of hippocampal neurons were established from embryonic rats （ day 18 of gestation）. The neurons were treated with CART at different doses （ 1, 10 and 100 nmol/L） and at different time points. The expression of phosphorylated ERK （ p - ERK） and BDNF were analyzed by Western blotting with or without PD98059, an ERK pathway inhibitor, treatment. RESULTS： CART increased expression of prolonged phosphorylated ERK in a time- and dose -dependent manner as compared with the controls（P〈0.01 ）, and also increased expression of BDNF, which was inhibited by PD98059 pretreatment. CONCLUSION： BDNF synthesis induced by CART is mediated through ERK activation in hippocampal neurons.