婴幼儿发育期全身麻醉药暴露对认知功能的影响及机制
赵欣^1,2, 郝利军^1,2,3, 张雨彤^1,2, 张宇^1,2, 张策^1,2,*
1山西医科大学生理学系，太原 030001；²山西医科大学细胞生理学教育部重点实验室，太原 030001；³ 山西省人民医院麻醉科，太原 030012
摘要
随着医疗技术的进步，各类先进设备、检测手段不断增加，通过手术或其他有创方式救治的疾病谱不断增加。越来越多的婴幼儿需要接受全身麻醉药(全麻药)麻醉进行临床检查或治疗，而全麻药是否对仍处在发育期的婴幼儿脑结构和功能(如认知)产生影响是一个重要、复杂而又有争议的问题，因而受到神经生物学、麻醉学和儿科学等领域****的高度关注。人群调查结果证实，发育期短期单次全麻药暴露对认知功能的影响较弱，多次全麻药暴露则会对认知功能造成损伤。基于动物的研究进一步揭示了发育期全麻药暴露的损伤机制。全麻药暴露的时间点较麻醉时长更关键，突触形成高峰期最易受全麻药损伤；在突触形成高峰期，全麻药暴露可诱导胞内钙超载、线粒体损伤、能量代谢失衡，损伤细胞功能；启动细胞凋亡，诱导过度自噬，导致细胞丢失；抑制突触相关蛋白的表达，突触形成受损，干扰突触传递过程及可塑性，影响神经环路和脑区功能活动。因此，细胞损伤、细胞丢失和神经环路功能受损构成发育期全麻药暴露损伤认知功能的重要机制。此外，有研究应用高通量组学技术对全麻药暴露引起的差异表达基因进行了初步筛选，为深入研究全麻药损伤的基因表达及调控机制提供了新思路。本文从整体行为学、神经元网络、细胞损伤、基因表达及调控和脑功能代谢等方面对发育期全麻药暴露影响认知功能及相关机制的研究进展进行综述，希望能为临床婴幼儿全麻方案的制定提供理论依据。


关键词： 全身麻醉药; 脑发育; 认知; 影响; 机制
分类号：R338;R614.2

Influence of general anesthetic exposure in developing brain on cognition and the underlying mechanisms
ZHAO Xin^1,2, HAO Li-Jun^1,2,3, ZHANG Yu-Tong^1,2, ZHANG Yu^1,2, ZHANG Ce^1,2,*
1Department of Physiology, Shanxi Medical University, Taiyuan 030001, China；²Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China；³ Department of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan 030012, China
Abstract
With the evolution of medical techniques and technology, an increasing number of infants, neonates, and fetuses are
exposed to general anesthesia for clinical diagnostic and therapeutic process. The neurotoxic effects of general anesthetics on developing brain have been a subject of concern and considerable research interest. Population-based study confirmed that single short-term general anesthetic exposure does not affect nervous system function, but multiple exposures to general anesthesia could damage cognitive function. Animal studies further discovered the underlying mechanisms. Nervous system is most susceptible to general anesthetics during the brain growth spurt. The time-point is more critical than the duration of exposure to general anesthetics. General anesthetics can induce intracellular calcium overload, disturb energy metabolism, promote cell apoptosis and lead to cell loss. General anesthetics can damage synaptic structure, transmission and plasticity, and impair brain function. High throughput omics technologies have been used to screen the differentially expressed genes induced by general anesthetics, which provide further understanding of the mechanism of general anesthetics affecting cognitive function. This review provides an update on the pathophysiologic mechanisms underlying the anesthesia-neurotoxicity, which will be helpful to provide instructions for the clinical use of general anesthesia in children.


Key words: general anesthetic; developing brain; cognitive; influence; mechanism

收稿日期：2019-01-15　　录用日期：2019-04-28
通讯作者：张策　　E-mail: cezh2002@yahoo.com
DOI: 10.13294/j.aps.2019.0048
引用本文：
赵欣, 郝利军, 张雨彤, 张宇, 张策. 婴幼儿发育期全身麻醉药暴露对认知功能的影响及机制[J]. 生理学报 2019; 71 (5): 749-759.
ZHAO Xin, HAO Li-Jun, ZHANG Yu-Tong, ZHANG Ce. Influence of general anesthetic exposure in developing brain on cognition and the underlying mechanisms. Acta Physiol Sin 2019; 71 (5): 749-759 (in Chinese with English abstract).



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