雌激素对β淀粉样蛋白（25-35）诱导大鼠皮质神经元细胞凋亡的影响

Effects of estrogen on βamyloid protein（25-35）-induced apoptosis in rat cortical neurons

目的研究雌激素抑制β淀粉样蛋白（Aβ）诱导大鼠神经细胞凋亡的作用机制。方法通过乳酸脱氢酶（LDH）释放率的测定及膜联蛋白V／碘化丙啶双染色流式细胞术观察17β-雌二醇（17β-E2）对Aβ（25～35）诱导的大脑皮质神经元细胞死亡及凋亡的影响，用半定量逆转录-聚合酶链反应（RT-PCR）方法检测Bcl-2在转录水平的表达。结果Aβ（25-35）可以诱导大鼠皮质神经元细胞凋亡，下调抗凋亡分子Bcl-2的表达。17β-E2预处理48h显著抑制Aβ（25～35）诱导的大鼠皮质神经元细胞凋亡，并且显著抑制Aβ（25-35）下调Bcl-2表达的作用。结论Aβ可以通过下调抗凋亡分子Bcl-2的表达诱导原代培养的大鼠皮质神经元细胞凋亡，雌激素可以通过上调抗凋亡分子Bcl-2的表达来抑制Aβ诱导的大鼠皮质神经元细胞凋亡。

Objective： To study the effect of estrogen on the apoptosis induced by β-amyloid protein（Aβ） in primary cultures of rat cortical neurons. Methods： The effect of 17β-E2 on Aβ（25-35）-induced cell death and apoptosis in primary culture of rat cortical neurons was observed by determination of lactate dehydrogenase（LDH） release rate and flow cytometry detection with AnnexinV/PI double-staining. The expression of Bcl-2 was determined by semiquantitative reverse transcription-polymerase chain reaction（RT-PCR）. Results： Aβ（25-35） induced cell death and apoptosis in primary culture of rat cortical neurons. It also down-regulated Bcl-2 gene expression. Pretreatment with 17β-E2 for forty eight hours protected rat cortical neurons from Aβ（25 - 35）-induced apoptosis, and inhibited Aβ （25 - 35）-induced down-regulation of Bcl-2 expression. Conclusions： The study indicates that Aβ induces apoptosis in the primary culture of rat cortical neurons through the down-regulation of Bcl-2. Estrogen has a protective effect against the apoptosis induced by Aβ（25-35） through up-regulation of antiapoptotic protein Bcl-2.