Martynyuk Anatoly E, Ju Ling-Sha, Morey Timothy E, Zhang Jia-Qiang
Department of Anesthesiology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, United States.
Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States.
World J Psychiatry. 2020 May 19;10(5):81-94. doi: 10.5498/wjp.v10.i5.81.
The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.
如果不使用全身麻醉剂（GAs），现代医学的进步将是不可能的。尽管在优化麻醉方法方面取得了进展，但全身麻醉剂的作用在停用后并非完全可逆。归因于全身麻醉剂暴露的神经认知缺陷在新生儿中可能持续存在，在老年人中可能持续数周甚至数年。需要对全身麻醉剂长期不良反应的机制进行人体研究，以提高全身麻醉的安全性，但这些研究不仅受到人体研究特有的伦理限制的阻碍，还受到缺乏可用于人体研究以安全、客观地研究此类影响的特定生物标志物的限制。后者主要可归因于对全身麻醉剂诱导的生物效应的全面范围以及介导此类效应的分子机制的理解不足，即使在啮齿动物中也是如此，而啮齿动物的研究比任何其他物种都要广泛得多。我们最近在啮齿动物中的实验结果表明，全身麻醉剂可能对更多人的影响比目前预期的要大。具体而言，我们已经表明，常用的全身麻醉剂七氟烷麻醉不仅会在暴露的动物中引起神经内分泌异常（躯体效应），还会引起生殖细胞的表观遗传重编程（生殖细胞效应）。后者可能将亲代七氟烷暴露的神经行为效应传递给后代，即使在对暴露的亲代无害的麻醉水平下，后代也可能受到影响。需要全身麻醉的患者数量众多，其未来未暴露的后代数量更多，其健康可能受到影响，以及越来越多病因不明的神经发育障碍，凸显了研究全身麻醉剂代际效应的转化重要性。在这篇小型综述中，我们讨论了关于全身麻醉剂的神经内分泌、表观遗传和代际效应的新出现的实验结果。
