Yu Zhiqiang, Zhao Qi, Duan Fangqi, Dong Yan, Zhang Li, Gao Jie, Chen Dongyan
Department of Anesthesiology, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology and Obstetrics, Nankai University Affiliated Hospital of Gynecology and Obstetrics, No. 156, Nankai Third Road, Nankai District, Tianjin, 300100, China.
Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, China.
Exp Brain Res. 2025 Mar 21;243(4):96. doi: 10.1007/s00221-025-07050-7.
To investigate the associations between the neurotoxicity of sevoflurane and the neuroprotection provided by dexmedetomidine, we measured apoptotic gene and protein expression, brain-derived neurotrophic factor (BDNF) levels, and receptor expression, and neuronal apoptosis. Pregnant rats were treated with dexmedetomidine, 2.5% sevoflurane for 6 h, or a combination of 2.5% sevoflurane for 6 h with dexmedetomidine on gestational day 18 (G18). The apoptotic genes and proteins expression, BDNF and receptor expression, and neuronal apoptosis were assessed in offspring hippocampi on postnatal day 1 (P1) and P41. Dendritic spine density, synaptophysin protein fluorescence staining, and cognitive function were evaluated on P41. Maternal sevoflurane exposure increased Bax mRNA and protein expression, decreased Bcl-2 mRNA and protein expression, enhanced neuronal apoptosis, decreased the ratio of mature BDNF (mBDNF) to proBDNF, reduced mBDNF and tropomyosin receptor kinase B (TrkB) protein expression, and increased p75 neurotrophin receptor (p75NTR) protein expression in the hippocampi of neonatal rats. In juvenile rats, maternal sevoflurane exposure reduced mBDNF and TrkB protein expression, dendritic spine density, the proportion of time spent in the target quadrant, and the number of crossings over the platform while increasing escape latency in the Morris water maze. All abnormalities induced by maternal sevoflurane exposure, except for mBDNF levels on P41, were alleviated by dexmedetomidine. Dexmedetomidine mitigates sevoflurane-induced neuronal development abnormalities and cognitive impairments during late pregnancy by improving hippocampal Bcl-2 and Bax mRNA and protein expression, as well as proBDNF-p75NTR and mBDNF-TrkB protein expression in offspring.
为了研究七氟醚的神经毒性与右美托咪定提供的神经保护之间的关联，我们测量了凋亡基因和蛋白表达、脑源性神经营养因子（BDNF）水平、受体表达以及神经元凋亡情况。在妊娠第18天（G18），对孕鼠分别给予右美托咪定、2.5%七氟醚6小时，或2.5%七氟醚6小时与右美托咪定联合处理。在出生后第1天（P1）和第41天（P41）评估子代海马中的凋亡基因和蛋白表达、BDNF和受体表达以及神经元凋亡情况。在P41评估树突棘密度、突触素蛋白荧光染色和认知功能。母体暴露于七氟醚会增加新生大鼠海马中Bax mRNA和蛋白表达，降低Bcl-2 mRNA和蛋白表达，增强神经元凋亡，降低成熟BDNF（mBDNF）与前体BDNF的比值，减少mBDNF和原肌球蛋白受体激酶B（TrkB）蛋白表达，并增加p75神经营养因子受体（p75NTR）蛋白表达。在幼鼠中，母体暴露于七氟醚会降低mBDNF和TrkB蛋白表达、树突棘密度、在目标象限花费的时间比例以及穿越平台的次数，同时增加在莫里斯水迷宫中的逃避潜伏期。除P41时的mBDNF水平外，右美托咪定可缓解母体暴露于七氟醚所诱导的所有异常情况。右美托咪定通过改善子代海马中Bcl-2和Bax mRNA及蛋白表达，以及前体BDNF-p75NTR和mBDNF-TrkB蛋白表达，减轻妊娠晚期七氟醚诱导的神经元发育异常和认知障碍。
