摘要目的:探讨可卡因－苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript, CART)对氧葡萄糖剥夺(oxygen-glucose deprivation, OGD)小鼠皮质神经元突触结构的影响。方法:选用健康清洁级昆明小鼠16～17 d孕龄胚胎大脑皮质进行原代神经元培养，分为对照组、CART组、OGD组以及OGD＋CART组。OGD＋CART组在OGD处理后加入0.4 nmol/L CART 55-102培养12 h；CART组予以等剂量CART 55-102。采用流式细胞术检测神经元死亡率。通过免疫荧光分析观察神经元突触结构变化，并对轴突长度和突触蛋白Ⅰ阳性面积进行定量分析。采用实时荧光定量聚合酶链反应和蛋白质印迹分析检测脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)mRNA和蛋白表达。 结果:与对照组比较，OGD组神经元死亡率显著增高，神经元突触生长明显受到抑制，突触蛋白Ⅰ阳性面积显著缩小，BDNF mRNA和蛋白表达水平显著下调( P均<0.05)。与OGD组比较，加入CART 55-102后能显著降低OGD神经元死亡率( P<0.05)，逆转OGD对神经元突触生长的抑制作用，使神经元轴突长度及突触蛋白Ⅰ阳性面积显著增大( P均<0.05)，并显著上调BDNF mRNA和蛋白表达水平( P均<0.05)。 结论:CART能保护OGD小鼠脑皮质神经元的突触结构，其机制可能与上调BDNF表达有关。

abstractsObjective:To investigate the effect of cocaine- and amphetamine-regulated transcript peptide (CART) on the synapse structure of mice cortical neuron subjected to oxygen-glucose deprivation (OGD).Methods:Primary neurons of the embryonic cerebral cortex obtained from healthy and clean Kunming mice at gestational age of 16-17 d were cultured. They were divided into control group, CART group, OGD group, and OGD+ CART group. 0.4 nmol/L CART 55-102 was added and cultured for 12 h after OGD treatment in the OGD+ CART group; the CART group was given the same dose of CART 55-102. The neuronal mortality was measured by the flow cytometry. The changes of synaptic structure were observed by immunofluorescence analysis, and the axon length and synapsin Ⅰ positive area were quantitatively analyzed. Real-time fluorescent quantitative polymerase chain reaction and Western blot analysis were used to identify the brain-derived neurotrophic factor (BDNF) mRNA and protein expression. Results:Compared with the control group, the mortality of neurons in the OGD group was significantly increased, the neuronal synapse growth was significantly inhibited, the positive area of synapsin Ⅰ was significantly reduced, and the expression levels of BDNF mRNA and protein were significantly down-regulated (all P<0.05). Compared with the OGD group, adding CART 55-102 significantly reduced the mortality of OGD neurons ( P<0.05), reversed the inhibitory effect of OGD on neuronal synapse growth, significantly increased the length of neuron axons and the positive area of synapsin Ⅰ (all P<0.05), and significantly up-regulated BDNF mRNA and protein expression levels (all P<0.05). Conclusion:CART can protect the synaptic structure of mice cortical neuron subjected to OGD, and its mechanism may be related to the up-regulation of BDNF expression.