Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry and can cause neurotoxicity; however, the underlying mechanism remains unclear. In the study, we found that DEHP significantly inhibited viability of mouse NE-4C neural stem cells and caused lactate dehydrogenase (LDH) release from the cells. DEHP dramatically increased the levels of apoptosis-related proteins such as cleaved Caspase-8, cleaved Caspase-3 and Bax, as well as decreased Bcl-2 protein level. DEHP could also significantly increase the total numbers of AnnexinV-positive/PI-negative and AnnexinV-positive/PI-positive staining cells. Hoechst 33342 staining showed that marked DNA condensation and apoptotic bodies could be found in the ZnO NPs-treated cells. These results indicated that DEHP could induce apoptosis of NE-4C cells. Meanwhile, DEHP could significantly increase malondialdehyde (MDA) level, and decrease the content of glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), respectively, implying that DEHP could induce oxidative stress of NE-4C cells. Furthermore, N-Acetyl-l-cysteine (NAC), an inhibitor of oxidative stress, could rescue the inhibition of cell viability and induction of apoptosis by DEHP. Taken together, our results showed that oxidative stress was involved in DEHP-induced apoptosis of mouse NE-4C cells.

邻苯二甲酸二-2-乙基己酯（DEHP）在工业上已被广泛用作增塑剂，并会引起神经毒性。但是，其潜在机制仍不清楚。在这项研究中，我们发现DEHP显着抑制小鼠NE-4C神经干细胞的活力并引起乳酸脱氢酶（LDH）从细胞中释放。DEHP显着增加了凋亡相关蛋白的水平，例如裂解的Caspase-8，裂解的Caspase-3和Bax，以及降低的Bcl-2蛋白水平。DEHP还可以显着增加AnnexinV阳性/ PI阴性和AnnexinV阳性/ PI阳性染色细胞的总数。Hoechst 33342染色表明，在用ZnO NPs处理的细胞中可以发现明显的DNA缩合和凋亡小体。这些结果表明DEHP可以诱导NE-4C细胞凋亡。同时，DEHP可以显着提高丙二醛（MDA）的水平，并分别降低谷胱甘肽（GSH）的含量和超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性，这表明DEHP可以诱导NE-4C细胞的氧化应激。此外，N-乙酰-1-半胱氨酸（NAC），一种氧化应激的抑制剂，可以挽救DEHP对细胞活力的抑制和凋亡的诱导。两者合计，我们的结果表明，氧化应激与DEHP诱导的小鼠NE-4C细胞凋亡有关。