摘要
高浓度的异丙酚可导致动物和人类发生脑损伤,而右美托咪定对多种脑损伤动物模型具有一定的神经保护作用。为了考察右美托咪定对异丙酚麻醉所致新生大鼠脑损伤的保护作用及机制,本研究对7日龄清洁级SD大鼠分别腹腔注射异丙酚(60 mg/kg)、右美托咪定(80μg/kg)和异丙酚(60 mg/kg)+右美托咪定(80μg/kg)。Morris水迷宫实验发现高剂量的异丙酚可显著增加大鼠的逃避潜伏期并减少穿越平台次数,然而右美托咪定预处理则可显著降低大鼠的逃避潜伏期并提高穿越平台次数(p<0.05)。异丙酚单独处理导致大鼠的海马神经元细胞凋亡程度显著增加,而右美托咪定预处理则可显著抑制神经元细胞的凋亡(p<0.05)。异丙酚单独处理可显著下调PSD95蛋白的表达,但右美托咪定预处理则可有效抑制PSD95蛋白的下调(p<0.05)。高剂量的异丙酚可明显下调大鼠海马组织P13K、Akt和GSK-3βmRNA的表达,而右美托咪定预处理则可抑制P13K、Akt和GSK-3βmRNA的下调。此外,右美托咪定预处理可显著提高p-Akt/Akt和p-GSK-3β/GSK-3β蛋白比值。本研究表明,右美托咪定可有效抑制异丙酚诱导的神经元细胞凋亡,改善大鼠的学习和记忆能力。右美托咪定的神经保护作用与其对PI3K/AKT/GSK-3β信号通路的激活有关。
High concentrations of propofol can cause brain damage in animals and humans, while dexmedetomidine has a certain neuroprotective effect on various animal models of brain injury. In order to investigate the protective effect and mechanism of dexmedetomidine on brain damage induced by propofol anesthesia in rats, propofol(60 mg/kg), dexmedetomidine(80 μg/kg) and propofol(60 mg/kg)+dexmedetomidine(80 μg/kg) were administered intraperitoneally to 7-day-old SD rats. Morris water maze experiments found that high doses of propofol significantly increased the escape latency of rats and reduced the number of platform crossing. However, dexmedetomidine pretreatment significantly reduced the escape latency of rats and increased the number of platform crossing(p<0.05).Propofol treatment alone resulted in a significant increase in the degree of apoptosis in rat hippocampal neurons,whereas dexmedetomidine pretreatment significantly inhibited neuronal cell apoptosis(p<0.05). Propofol treatment alone significantly down-regulated the expression of PSD95 protein, but dexmedetomidine pretreatment significantly inhibited the down-regulation of PSD95 protein(p<0.05). High dose of propofol significantly down-regulated the expression of P13K, Akt and GSK-3β mRNA in rat hippocampus, while dexmedetomidine pretreatment inhibited the down-regulation of P13K, Akt and GSK-3β mRNA. In addition, dexmedetomidine pretreatment significantly increased the ratio of p-Akt/Akt and p-GSK-3β/GSK-3β protein. This study shows that dexmedetomidine can effectively inhibit propofol-induced neuronal apoptosis and improve learning and memory in rats. The neuroprotective effect of dexmedetomidine is related to its activation of the PI3K/AKT/GSK-3β signaling pathway.
作者
王昕
吴向群
刘祥
Wang Xin;Wu Xiangqun;Liu Xiang(The Second People's Hospital of Hefei,Hefei,230011)
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2020年第3期1275-1282,共8页
Genomics and Applied Biology
