氧化应激
血红素加氧酶
右美托咪定
神经保护
异氟醚
医学
激酶
标记法
蛋白激酶A
药理学
内分泌学
神经毒性
莫里斯水上航行任务
内科学
MAPK/ERK通路
麻醉
血红素
化学
海马体
毒性
生物化学
免疫组织化学
镇静
酶
作者
Hai-Jin Huang,Yunsheng Zhu,Yang Zhang,Ben-Chao Hou,Qin Zhang,Xiao-Yun Shi,Jia Min
标识
DOI:10.1016/j.cbi.2022.110114
摘要
Dexmedetomidine (DEX) displays a neuroprotective role in aged rats with isoflurane (ISO)-induced cognitive impairment through antioxidant, and anti-inflammatory, and anti-apoptotic effects. Therefore, the present study was performed to define the molecular mechanism of DEX on ISO-induced neurological impairment in aged rats in relation to the MEK1/ERK1/Nrf2/HO-1 axis. The study enrolled elderly patients undergoing ISO anesthesia. Patient cognitive function following treatment with DEX was evaluated using mini-mental state examination (MMSE). The results revealed that DEX supplementation of anesthesia contributed to higher MMSE scores in patients one week post treatment. Rat model of neurological impairment was also induced in 18-month-age Wistar rats by ISO, followed by DEX treatment. Based on the results of Morris water maze experiment, ELISA, and TUNEL and hematoxylin-eosin staining, in vivo experiments confirmed that DEX could reduce the oxidative stress and neurological damage induced by ISO in rats. DEX activated the nuclear factor erythroid 2-related factor (Nrf2)/Heme Oxygenase 1 (HO-1) pathway. DEX upregulated the expression of Nrf2 and HO-1 by activating the MEK1/ERK1 pathway, whereby attenuating the ISO-caused oxidative stress and neurological damage in rats. Collectively, DEX suppresses the ISO-induced neurological impairment in the aged rats by promoting HO-1 through activation of the MEK1/ERK1/Nrf2 axis.
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