异氟醚对人神经祖细胞增殖、分化和存活的双重影响。
Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.
机构信息
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
Anesthesiology. 2013 Mar;118(3):537-49. doi: 10.1097/ALN.0b013e3182833fae.
BACKGROUND
Previous studies have demonstrated that isoflurane can provide both neuroprotection and neurotoxicity in various tissue culture models and in rodent developing brains. The cellular and molecular mechanisms mediating these dual effects are not clear, but the exposure level and duration of isoflurane appear to be determinant factors.
METHODS
Using the ReNcell CX (Millipore, Billerica, MA) human neural progenitor cell line, the authors investigated the impact of prolonged exposure to varying isoflurane concentrations on cell survival and neurogenesis. In addition, the authors assessed the impact of short isoflurane preconditioning on elevation of cytosolic Ca concentration and cytotoxic effects mediated by prolonged isoflurane exposures and the contribution of inositol-1,4,5-trisphosphate or ryanodine receptor activation to these processes.
RESULTS
Short exposures to low isoflurane concentrations promote proliferation and differentiation of ReNcell CX cells, with no cell damage. However, prolonged exposures to high isoflurane concentrations induced significant ReNcell CX cell damage and inhibited cell proliferation. These prolonged exposures suppressed neuronal cell fate and promoted glial cell fate. Preconditioning of ReNcell CX cultures with short exposures to low concentrations of isoflurane ameliorated the effects of prolonged exposures to isoflurane. Pretreatment of ReNcell cultures with inositol-1,4,5-trisphosphate or ryanodine receptor antagonists mostly prevented isoflurane-mediated effects on survival, proliferation, and differentiation. Finally, isoflurane-preconditioned cultures showed significantly less isoflurane-evoked changes in calcium concentration.
CONCLUSION
The commonly used general anesthetic isoflurane exerts dual effects on neuronal stem cell survival, proliferation, and differentiation, which may be attributed to differential regulation of calcium release through activation of endoplasmic reticulum localized inositol-1,4,5-trisphosphate and/or ryanodine receptors.
背景
先前的研究表明，异氟醚在各种组织培养模型和啮齿动物发育大脑中均可提供神经保护和神经毒性。介导这些双重作用的细胞和分子机制尚不清楚，但异氟醚的暴露水平和持续时间似乎是决定因素。
方法
作者使用 ReNcell CX（Millipore，Billerica，MA）人神经祖细胞系，研究了长时间暴露于不同异氟醚浓度对细胞存活和神经发生的影响。此外，作者评估了短暂异氟醚预处理对延长异氟醚暴露引起的细胞溶质 Ca 浓度升高和细胞毒性作用的影响，以及肌醇 1,4,5-三磷酸或 Ryanodine 受体激活对这些过程的贡献。
结果
短暂暴露于低浓度异氟醚可促进 ReNcell CX 细胞的增殖和分化，而不会造成细胞损伤。然而，长时间暴露于高浓度异氟醚会导致 ReNcell CX 细胞明显损伤并抑制细胞增殖。这些长时间暴露会抑制神经元细胞命运并促进神经胶质细胞命运。用短暂暴露于低浓度异氟醚预处理 ReNcell CX 培养物可改善长时间暴露于异氟醚的作用。用肌醇 1,4,5-三磷酸或 Ryanodine 受体拮抗剂预处理 ReNcell 培养物可在很大程度上阻止异氟醚对存活、增殖和分化的影响。最后，异氟醚预处理培养物显示出明显较少的异氟醚引起的钙浓度变化。
结论
常用的全身麻醉剂异氟醚对神经干细胞的存活、增殖和分化具有双重作用，这可能归因于内质网中肌醇 1,4,5-三磷酸和/或 Ryanodine 受体的激活对钙释放的差异调节。
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