Yin Xiaoxu, Jiang Peng, Li Jing
Department of Anesthesiology, Huizhou Central People's Hospital, Huizhou, Guangdong 516001, China.
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710038, China.
Evid Based Complement Alternat Med. 2022 May 31;2022:9543459. doi: 10.1155/2022/9543459. eCollection 2022.
General anesthesia in early childhood may affect all aspects of neurodevelopment, resulting in learning and behavior defects. Therefore, there is an urgent need to find safe anesthetics or put forward more comprehensive anesthesia schemes to solve the negative effects caused by existing anesthetics. The objective of this study is to explore the impact of dexmedetomidine (Dex) incorporated with low-dose propofol (PRO) on learning and memory ability and neural cells in developing rats.
Eighty SD rats were randomly divided into 4 groups including the Sham group, Lipid group, L-PRO group, and Dex + L-PRO group. After treatment, the spatial learning and memory ability of rats in each group were assessed by the water maze test and the passive avoidance test. The damage of hippocampal tissues was assessed by Nissl staining; the apoptosis, the levels of inflammatory factors, and the level of oxidative stress were measured by Tunel staining, ELISA, and biochemical assays, respectively. Besides, qRT-PCR and Western Blot determined the expression of apoptosis-related proteins, neurotrophic factors, and MAPK signaling pathway-related proteins in the hippocampus.
Compared with the L-PRO group, the Dex + L-PRO group had better spatial learning and memory ability. Administration of Dex and L-PRO greatly alleviated neural cell damage in the hippocampus and decreased the levels of IL-6, IL-1, and TNF-. Besides, it significantly decreased the content of ROS and malondialdehyde (MDA), glutathione (GSH), when up-regulating the levels of IL-10, antioxidant superoxide dismutase (SOD) and BDNF, receptor tyrosine kinase B (TrkB), and neurotrophin-3 (NT-3) related to hearing function and significantly lower activity of MAPK signaling pathway.
Dex combined with low-dose PRO can significantly inhibit inflammation, oxidative stress response, neuronal apoptosis, MAPK signaling pathway activity and promote the secretion of neurokines in hippocampus to reduce neural cell damage and avoid the learning and memory impairment caused by anesthetics in developing rats.
幼儿期全身麻醉可能会影响神经发育的各个方面,导致学习和行为缺陷。因此,迫切需要寻找安全的麻醉剂或提出更全面的麻醉方案,以解决现有麻醉剂所造成的负面影响。本研究的目的是探讨右美托咪定(Dex)联合低剂量丙泊酚(PRO)对发育中大鼠学习记忆能力及神经细胞的影响。
80只SD大鼠随机分为4组,包括假手术组、脂质组、L-PRO组和Dex+L-PRO组。处理后,通过水迷宫试验和被动回避试验评估各组大鼠的空间学习和记忆能力。通过尼氏染色评估海马组织的损伤;分别通过Tunel染色、ELISA和生化检测测定细胞凋亡、炎症因子水平和氧化应激水平。此外,qRT-PCR和蛋白质免疫印迹法检测海马中凋亡相关蛋白、神经营养因子和MAPK信号通路相关蛋白的表达。
与L-PRO组相比,Dex+L-PRO组具有更好的空间学习和记忆能力。给予Dex和L-PRO可显著减轻海马神经细胞损伤,并降低IL-6、IL-1和TNF-水平。此外,它还显著降低了活性氧(ROS)和丙二醛(MDA)含量,提高了谷胱甘肽(GSH)水平,同时上调了与听力功能相关的IL-10、抗氧化超氧化物歧化酶(SOD)和脑源性神经营养因子(BDNF)、受体酪氨酸激酶B(TrkB)以及神经营养因子-3(NT-3)水平,且MAPK信号通路活性显著降低。
Dex联合低剂量PRO可显著抑制炎症、氧化应激反应、神经元凋亡、MAPK信号通路活性,并促进海马中神经因子的分泌,以减少神经细胞损伤,避免发育中大鼠因麻醉剂导致的学习记忆障碍。