N-硬脂酰酪氨酸对缺氧缺糖诱导神经元凋亡的影响

Neuroprotective effects of NsTyr against OGD-induced apoptosis on cortical neurons

目的探讨N-硬脂酰酪氨酸(NsTyr)对缺氧缺糖(OGD)诱导大鼠皮层神经元损伤的影响及作用机制。方法采用MTT法及Hoechst 33342染色检测NsTyr对OGD诱导神经元损伤及凋亡的影响;通过免疫印迹法探讨NsTyr抗OGD诱导神经元凋亡的分子机制,并使用丝裂原活化蛋白激酶(MAPK)通路的特异性阻断剂SB203580、SP600125和U0126考察其抗凋亡的信号转导通路。结果 NsTyr对OGD造成的皮层神经元损伤有剂量相关的保护作用,促进细胞存活,减少细胞凋亡;NsTyr通过上调Bcl-2表达、下调Bax表达、保持Bcl-2/Bax的平衡,实现抗OGD损伤的作用,该作用通过ERK和p38信号通路介导。结论 NsTyr可通过ERK和p38信号通路调节凋亡基因的表达,抑制OGD引起的神经元凋亡。

Objective To investigate the protective effects apoptosis on primary cultured rat＇s cortical neurons. Methods ofN-stearoyltyrosine （NsTyr） against OGD-induced Cell death was evaluated with MTT assay, and the neuron apoptosis was analyzed through Hoechst staining. The mechanism and the signal pathways involved were studied by western blot analysis and the treatment of specific MAPK inhibitors. Results NsTyr alleviated does-dependently the OGD-induced toxicity to cortical neurons. The protection of NsTyr was through reversing the up-regulation of Bax and down-regulation of Bcl-2. Moreover, the effect was blocked by SB203580 and U0126, while no obvious influence on the regulation of Bcl-2 by SP600125 was observed. Conclusion NsTyr possesses protective effects on cortical neurons by regulating the balance between Bax and Bcl-2 through ERK and p38 signaling pathways.