摘 要：目的 探討 N-硬脂酰酪氨酸（NsTyr）對(duì)缺氧缺糖（OGD）誘導(dǎo)大鼠皮層神經(jīng)元損傷的影響及作用機(jī)制。方法 采用 MTT 法及 Hoechst 33342染色檢測 NsTyr 對(duì) OGD 誘導(dǎo)神經(jīng)元損傷及凋亡的影響；通過免疫印跡法探討 NsTyr 抗 OGD 誘導(dǎo)神經(jīng)元凋亡的分子機(jī)制，并使用絲裂原活化蛋白激酶（MAPK）通路的特異性阻斷劑 SB203580、SP600125和 U0126考察其抗凋亡的信號(hào)轉(zhuǎn)導(dǎo)通路。結(jié)果 NsTyr 對(duì) OGD 造成的皮層神經(jīng)元損傷有劑量相關(guān)的保護(hù)作用，促進(jìn)細(xì)胞存活，減少細(xì)胞凋亡；NsTyr 通過上調(diào) Bcl-2表達(dá)、下調(diào) Bax 表達(dá)、保持 Bcl-2/Bax 的平衡，實(shí)現(xiàn)抗 OGD 損傷的作用，該作用通過 ERK 和 p38信號(hào)通路介導(dǎo)。結(jié)論 NsTyr 可通過 ERK 和 p38信號(hào)通路調(diào)節(jié)凋亡基因的表達(dá)，抑制 OGD 引起的神經(jīng)元凋亡。

Abstract: Objective To investigate the protective effects of N-stearoyltyrosine（NsTyr）against OGD-induced apoptosis on primary cultured rat′s cortical neurons．Methods 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．

國家自然科學(xué)基金資助項(xiàng)目（30672441，30873057）；上海市科委基礎(chǔ)重點(diǎn)課題（08JC1413600）；十一五“重大新藥創(chuàng)制”科技重大專項(xiàng)“綜合性新藥研究開發(fā)技術(shù)大平臺(tái)”（2009ZX09301-007）