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目的:探讨咪达唑仑对被剥夺氧和葡萄糖(oxygen-glucose deprivation，OGD)后的N2a/APP695细胞淀粉样前体蛋白(amyloid precursor protein，APP)代谢变化的影响及机制。方法:将处于对数生长期的N2a/APP695细胞用平衡盐缓冲液冲洗后随机分为空白组、对照组及实验组。空白组未经OGD处理，在正常培养箱内培养；对照组行OGD处理后继续培养复氧；实验组在OGD处理后加入不同浓度(分别为70、100、125、150 ng/ml)的咪达唑仑继续培养复氧。24 h后用AnnexinV-FITC/双染法流式细胞术检测各组细胞凋亡比例；用Western blot方法检测各组细胞的Caspase-3、Aβn 1-42、解整合素金属蛋白酶10(adisintegrin and metalloproteinase 10，ADAM10)、β-淀粉样前体蛋白水解酶1(β-site APP cleavage enzyme-1，BACE1)、早老素1(presenilin 1，PS1)蛋白水平。n 结果:与空白组相比，对照组的细胞凋亡比例、Caspase-3、Aβn 1-42、BACE1及PS1水平显著升高(n P0.05)。与对照组相比，实验组细胞凋亡比例、Caspase-3、Aβn 1-42显著下降(n P<0.05)；咪达唑仑70 ng/ml组BACE1显著下降(n P0.05)。n 结论:OGD可通过上调BACE1及PS-1导致Aβn 1-42表达增加促使细胞凋亡；而咪达唑仑可通过下调BACE1减少Aβn 1-42表达进而减少神经细胞凋亡，发挥对OGD损伤后N2a/APP695细胞的保护作用。n “,”Objective:To study the inhibitory effects and mechanisms of midazolam on amyloid precursor protein (APP) in N2a/APP695 cells after oxygen-glucose deprivation (OGD).Method:N2a/APP695 cells in logarithmic growth phase were rinsed with Earle’s Balanced Salt Buffer (EBSS) and randomly assigned into blank group, control group and experimental group. The blank group was cultured in a normal incubator without OGD treatment. The control group was reoxygenated after OGD treatment. The experimental group was reoxygenated and added different concentrations (70, 100, 125, 150 ng/ml) of midazolam after OGD treatment. Twenty-four hours later, the apoptosis rate of the three groups was detected using AnnexinV-FITC/double staining flow cytometry. Western blot was used to detect Caspase-3, Aβ1-42, adisintegrin and metalloproteinase 10 (ADAM10), β-site APP cleavage enzyme-1 (BACE1), and presenilin 1 (PS1) protein levels.Result:Compared with the blank group, the percentage of apoptosis, the levels of Caspase-3, Aβn 1-42, BACE1 and PS1 in the control group were significantly increased (n P0.05). Compared with the control group, the proportion of apoptosis, the levels of Caspase-3 and Aβn 1-42 decreased significantly in the experimental group. The level of BACE1 decreased significantly in midazolam 70 ng/ml group (n P0.05).n Conclusion:OGD can up-regulate the levels of BACE1 and PS-1 to increase Aβn 1-42 expression to promote apoptosis. Midazolam can down-regulate BACE1 to reduce the expression of Aβn 1-42 thus reducing the apoptosis of nerve cells, and play a protective role in N2a/APP695 cells after OGD injury.n