Wei Huafeng, Xie Zhongcong
Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Alzheimer Res. 2009 Feb;6(1):30-5. doi: 10.2174/156720509787313934.
While anesthetics are indispensable clinical tools generally safe and effective, in some situations there is grown concern about selective neurotoxicity of these agents; the clinical significance is unclear as of yet. The mechanisms for inhalational anesthetics mediated cell damage are still not clear, although a role for calcium dysregulation has been suggested. For example, the inhaled anesthetic isoflurane decreases endoplasmic reticulum (ER) calcium concentration and increases that in the cytosol and mitochondria. Inhibition of ER calcium release, via either IP(3) or ryanodine receptors, significantly inhibited isoflurane neurotoxicity. Neurons made vulnerable to calcium dysregulation by overexpression of mutated presenilin-1 (PS1) or huntingtin (Q-111) proteins showed enhanced apoptosis upon isoflurane exposure. Sevoflurane and desflurane were less potent than isoflurane in altering intracellular calcium, and produced less apoptosis. Short exposures to inhalational anesthetics may provide neuroprotection by preconditioning via a sublethal stress, while prolonged exposures to inhalational anesthetics may induce cell damage by apoptosis through direct cytotoxic effects.
虽然麻醉剂是不可或缺的临床工具，总体上安全有效，但在某些情况下，人们越来越关注这些药物的选择性神经毒性；其临床意义目前尚不清楚。吸入性麻醉剂介导细胞损伤的机制仍不明确，尽管有人提出钙调节异常起了作用。例如，吸入性麻醉剂异氟烷可降低内质网（ER）钙浓度，并增加细胞质和线粒体中的钙浓度。通过IP(3)或兰尼碱受体抑制ER钙释放，可显著抑制异氟烷的神经毒性。通过突变早老素-1（PS1）或亨廷顿蛋白（Q-111）的过表达而对钙调节异常敏感的神经元，在接触异氟烷后凋亡增加。七氟烷和地氟烷在改变细胞内钙方面的作用比异氟烷弱，且诱导的凋亡较少。短时间接触吸入性麻醉剂可能通过亚致死性应激预处理提供神经保护，而长时间接触吸入性麻醉剂可能通过直接细胞毒性作用诱导细胞凋亡，从而导致细胞损伤。
