期刊
ANESTHESIOLOGY
卷 111, 期 4, 页码 741-752出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e3181b27fd4
关键词
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资金
- NIA NIH HHS [R21 AG029856-01A2, R21 AG029856] Funding Source: Medline
- NIGMS NIH HHS [R01 GM088801, R01 GM088801-01A1] Funding Source: Medline
- NINDS NIH HHS [K08 NS048140, K08 NS048140-04, K08 NS048140-05] Funding Source: Medline
Background: Some anesthetics have been suggested to induce neurotoxicity, including promotion of Alzheimer's disease neuro-pathogenesis. Nitrous oxide and isoflurane are common anesthetics. The authors set out to assess the effects of nitrous oxide and/or isoflurane on apoptosis and beta-amyloid (A beta) levels in H4 human neuroglioma cells and primary neurons from naive mice. Methods: The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and Methods: The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and conditioned media were harvested at the end of the treatment. Caspase-3 activation, apoptosis, processing of amyloid precursor protein, and A beta levels were determined. Results: Treatment with a combination of 70% nitrous oxide and 1% isoflurane for 6 h induced caspase-3 activation and apoptosis In H4 naive cells and primary neurons from naive mice. The 70% nitrous oxide plus 1% isoflurane, but neither alone, for 6 h Induced caspase-3 activation and apoptosis, and increased levels of beta-site amyloid precursor protein-cleaving enzyme and A beta in H4-amyloid precursor protein cells. In addition, the nitrous oxide plus isoflurane-induced A beta generation was reduced by a broad caspase inhibitor, Z-VAD. Finally, the nitrous oxide plus isoflurane-induced caspase-3 activation was attenuated by gamma-secretase inhibitor L-685,458, but potentiated by exogenously added A beta. Conclusion: These results suggest that the common anesthetics nitrous oxide plus isoflurane may promote neurotoxicity by inducing apoptosis and increasing A beta levels. The generated A beta may further potentiate apoptosis to form another round of apoptosis and A beta generation. More studies, especially the in vivo confirmation of these in vitro findings, are needed.
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