Department of Anesthesiology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang-050000, China.
Curr Neurovasc Res. 2020;17(2):164-170. doi: 10.2174/1567202617666200217105109.
Iron homeostasis disorder and neuroinflammation are the most commonly known factors that promote the occurrence and development of cognitive impairment in people. Dexmedetomidine has an anti-inflammatory effect, and it reduces the incidence of postoperative cognitive dysfunction. Therefore, the aim of this study is to verify whether dexmedetomidine could improve lipopolysaccharide-induced iron homeostasis disorder in aged mice, and show neuroprotective effect.
First part, forty 12 month old male Kunming(KM) mice were divided into group N and group D: Normal saline group (group N), Dexmedetomidine group (group D). Second part, sixty 12-month-old male KM mice were divided into the following three groups: Normal saline group (group N), Lipopolysaccharide group (group LPS) and Dexmedetomidine + Lipopolysaccharide group (group D + LPS). The mice in group D + LPS were given dexmedetomidine, and given LPS intraperitoneally 2 h later. Mice underwent an oriented navigation test and a space exploration test in the Morris Water maze (MWM) test. The expression levels of Interleukin-6 ( IL-6), L-ferritin (FTL) and Transferrin receptor-1 (TfR1) in hippocampus were detected by the Western blot analysis; the hippocampal hepcidin mRNA was detected by Real-time PCR(RT-PCR); the reactive oxygen species (ROS) in the hippocampus was measured using ROS test kit.
Dexmedetomidine improved the cognitive decline induced by LPS. Dexmedetomidine reduced the level of hippocampal IL-6, and it attenuated the increase in their levels caused by LPS. It had no effect on hippocampal hepcidin mRNA, FTL, TfR1 and ROS but it could attenuate the increase caused by LPS.
Dexmedetomidine has no effect on iron metabolism pathway, but it can improve the cognitive decline and the iron disorder by reducing neuroinflammation and oxidative stress. The research indicates that dexmedetomidine plays a neuroprotective role.
铁稳态紊乱和神经炎症是最常见的促进认知障碍发生和发展的因素。右美托咪定具有抗炎作用，可降低术后认知功能障碍的发生率。因此，本研究旨在验证右美托咪定是否能改善衰老小鼠脂多糖诱导的铁稳态紊乱，并表现出神经保护作用。
第一部分，将 40 只 12 月龄雄性昆明（KM）小鼠分为 N 组和 D 组：生理盐水组（N 组），右美托咪定组（D 组）。第二部分，将 60 只 12 月龄雄性 KM 小鼠分为以下三组：生理盐水组（N 组），脂多糖组（LPS 组）和右美托咪定+脂多糖组（D+LPS 组）。D+LPS 组给予右美托咪定，2 小时后给予 LPS 腹腔注射。各组小鼠行 Morris 水迷宫（MWM）定向航行试验和空间探索试验。Western blot 检测海马组织白细胞介素 6（IL-6）、L 铁蛋白（FTL）和转铁蛋白受体 1（TfR1）的表达水平；实时荧光定量 PCR（RT-PCR）检测海马组织铁调素 mRNA；ROS 试剂盒检测海马组织活性氧（ROS）。
右美托咪定改善 LPS 诱导的认知下降。右美托咪定降低海马 IL-6 水平，并减轻 LPS 引起的其水平升高。对海马铁调素 mRNA、FTL、TfR1 和 ROS 无影响，但可减轻 LPS 引起的升高。
右美托咪定对铁代谢途径无影响，但通过减少神经炎症和氧化应激可改善认知下降和铁紊乱。研究表明右美托咪定具有神经保护作用。
