The mechanisms underlying propofol-induced toxicity in developing neurons are still unclear. The aim of present study was to explore the role of Pink1 mediated mitochondria pathway in propofol-induced developmental neurotoxicity. The primary Neural Stem Cells (NSCs) were isolated from the hippocampus of E15.5 mice embryos and then treated with propofol. The effects of propofol on proliferation, differentiation, apoptosis, mitochondria ultrastructure and MMP of NSCs were investigated. In addition, the abundance of Pink1 and a group of mitochondria related proteins in the cytoplasm and/or mitochondria were investigated, which mainly included CDK1, Drp1, Parkin1, DJ-1, Mfn1, Mfn2 and OPA1. Moreover, the relationship between Pink1 and these molecules was explored using gene silencing, or pretreatment with protein inhibitors. Finally, the NSCs were pretreated with mitochondrial specific antioxidant (MitoQ) or Drp1 inhibitor (Mdivi-1), and then the toxic effects of propofol on NSCs were investigated. Our results indicated that propofol treatment inhibited NSCs proliferation and division, and promoted NSCs apoptosis. Propofol induced significant NSCs mitochondria deformation, vacuolization and swelling, and decreased MMP. Additional studies showed that propofol affected a group of mitochondria related proteins via Pink1 inhibition, and CDK1, Drp1, Parkin1 and DJ-1 are the important downstream proteins of Pink1. Finally, the effects of propofol on proliferation, differentiation, apoptosis, mitochondrial ultrastructure and MMP of NSCs were significantly attenuated by MitoQ or Mdivi-1 pretreatment. The present study demonstrated that propofol regulates the proliferation, differentiation and apoptosis of NSCs via Pink1mediated mitochondria pathway.

丙泊酚在发育中的神经元中引起毒性的机制尚不清楚。本研究的目的是探讨 Pink1 介导的线粒体通路在丙泊酚诱导的发育神经毒性中的作用。从 E15.5 小鼠胚胎的海马体中分离出原代神经干细胞 (NSC)，然后用丙泊酚处理。研究丙泊酚对NSCs增殖、分化、凋亡、线粒体超微结构和MMP的影响。此外，研究了细胞质和/或线粒体中 Pink1 和一组线粒体相关蛋白的丰度，主要包括 CDK1、Drp1、Parkin1、DJ-1、Mfn1、Mfn2 和 OPA1。此外，使用基因沉默或用蛋白质抑制剂预处理来探索 Pink1 与这些分子之间的关系。最后，用线粒体特异性抗氧化剂（MitoQ）或Drp1抑制剂（Mdivi-1）对NSCs进行预处理，然后研究丙泊酚对NSCs的毒性作用。我们的结果表明，丙泊酚处理抑制了 NSCs 的增殖和分裂，并促进了 NSCs 的凋亡。丙泊酚诱导显着的 NSCs 线粒体变形、空泡化和肿胀，并降低 MMP。其他研究表明，丙泊酚通过抑制 Pink1 影响一组线粒体相关蛋白，CDK1、Drp1、Parkin1 和 DJ-1 是 Pink1 的重要下游蛋白。最后，MitoQ或Mdivi-1预处理显着减弱了丙泊酚对NSCs增殖、分化、凋亡、线粒体超微结构和MMP的影响。本研究表明，丙泊酚调节增殖，