Ma Guanqi, Wang Yueyuan, Guan Jinping, Li Cui, Ma Tengfei, Gao Xuzhu, Zhang Junlong
Department of Anesthesiology, Lianyungang Clinical College of Xuzhou Medical University, Lianyungang, China.
School of Pharmacy, Nanjing Medical University, Nanjing, China.
Anesthesiology. 2025 Oct 1;143(4):894-905. doi: 10.1097/ALN.0000000000005627. Epub 2025 Jun 19.
The release of synaptic neurotransmitters and function of presynaptic proteins are essential for maintaining nervous system excitation. General anesthesia is a reversible state characterized by the loss of consciousness and reduced responsiveness. This study hypothesized that polymorphisms in one or more genes encoding the three presynaptic proteins composing the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complex affect consciousness and autonomic nerve function during propofol anesthesia.
One hundred thirty preoperative patients volunteered to undergo a simulated anesthesia procedure. The participants were genotyped for candidate single-nucleotide polymorphisms using the Sanger method. Changes in verbal commands, eyelash reflexes, and the ability to hold a weighted object during anesthesia induction and recovery were recorded. Further, other anesthesia endpoints such as effector compartment concentrations (Ce), Bispectral Index (BCP-100; Beijing slgo Medical Technology Co., Ltd., China), heart rate variability, and peripheral perfusion index were explored based on the polymorphic site of significant differences in consciousness.
The median and interquartile range results show that the recovery time of verbal commands of the synaptosome-associated protein 25 (SNAP-25) rs6039822 G/G genotype (G/G vs . A/A, 319 [259 to 378] vs . 379 [318 to 466] s; P = 0.048) were shorter. Logistic regression analysis showed that SNAP-25 rs6039822 and sex were independent factors influencing the recovery of verbal commands (chi-square = 11.916; P = 0.008). Other consciousness indices, Ce, heart rate variability, and peripheral perfusion index, support the resistance of the SNAP-25 rs6039822 variant to anesthetic during recovery.
Genetic variation in SNAP-25 gene is associated with the recovery of consciousness and autonomic nervous system activity during propofol anesthesia. This finding supports that the presynaptic proteins may be related to the mechanism of action of propofol.
突触神经递质的释放和突触前蛋白的功能对于维持神经系统的兴奋至关重要。全身麻醉是一种以意识丧失和反应性降低为特征的可逆状态。本研究假设，编码可溶性N - 乙基马来酰亚胺敏感融合附着蛋白受体（SNARE）复合体的三种突触前蛋白的一个或多个基因中的多态性会影响丙泊酚麻醉期间的意识和自主神经功能。
130例术前患者自愿接受模拟麻醉程序。采用桑格法对参与者的候选单核苷酸多态性进行基因分型。记录麻醉诱导和恢复期间对语言指令、睫毛反射以及握持重物能力的变化。此外，基于意识方面存在显著差异的多态性位点，探索了其他麻醉终点指标，如效应室浓度（Ce）、脑电双频指数（BCP - 100；北京速眠医疗科技有限公司，中国）、心率变异性和外周灌注指数。
中位数和四分位间距结果显示，突触小体相关蛋白25（SNAP - 25）rs6039822 G/G基因型（G/G与A/A相比，319 [259至378]秒与379 [318至466]秒；P = 0.048）的语言指令恢复时间较短。逻辑回归分析表明，SNAP - 25 rs6039822和性别是影响语言指令恢复的独立因素（卡方 = 11.916；P = 0.008）。其他意识指标、Ce、心率变异性和外周灌注指数，均支持SNAP - 25 rs6039822变异体在恢复期间对麻醉的抵抗性。
SNAP - 25基因的遗传变异与丙泊酚麻醉期间的意识恢复和自主神经系统活动相关。这一发现支持突触前蛋白可能与丙泊酚的作用机制有关。
