Gao Wei, Lv Xue, Li Hao, Yan Xu-Sheng, Huo Dong-Sheng, Yang Zhan-Jun, Zhang Zhi-Guo, Jia Jian-Xin
Department of Anesthesiology, The Third Hospital of Baogang Group, Baotou, China.
Department of Human Anatomy, Baotou Medical College, Baotou, China.
J Toxicol Environ Health A. 2025;88(13):546-556. doi: 10.1080/15287394.2025.2469088. Epub 2025 Feb 24.
Cerebral ischemia-reperfusion injury (CIRI) is a prevalent clinical complication associated with reperfusion following ischemic stroke resulting in neuronal damage and cognitive impairment. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist with sedative, and analgesic properties, is frequently utilized as a sedative anesthetic in clinical surgeries, and believed to play a crucial role in the prognosis of patients suffering from CIRI. However, the mechanism underlying DEX in CIRI remains to be determined. This study aimed to investigate the neuroprotective effects of Dex in rats suffering from CIRI. In the treatment group, DEX (50 µg/kg) was administered intraperitoneally 30 min prior to surgery. Middle cerebral artery occlusion (MCAO) used as a model of CIRI occurred with cerebral artery occlusion for 2 h was followed by reperfusion with blood for 24, 72, 120 or 168 h. Neurological function as assessed by the Longa neurological function score test demonstrated significantly reduced neurological scores and increased % infarct size in MCAO group which was blocked by DEX suggesting that DEX might be effective in treating ischemic stroke. In the MCAO animals, 2,3,5-triphenyltetrazolium chloride (TTC) showed large marked areas of cerebral infarction which were diminished in size by DEX. Using Western blot analysis, results showed that in MCAO rats protein expression levels of TNF-α and IL-6 were increased accompanied by reduced protein expression levels of PI3K/AKT signaling pathway. DEX pretreatment reversed the effects of MCAO as evidenced by decrease in protein expression levels of TNF-α and IL-6 associated with elevated protein expression levels of PI3K/AKT/NF-κB signaling pathway. Data demonstrated that DEX pretreatment improved the neuromotor performance and cognitive functions in animals suffering from consequences of MCAO by diminishing inflammation and activation of the PI3K/AKT/NF-κB signaling pathway.
脑缺血再灌注损伤（CIRI）是一种常见的临床并发症，与缺血性中风后的再灌注相关，会导致神经元损伤和认知障碍。右美托咪定（DEX）是一种具有镇静和镇痛特性的高选择性α2肾上腺素能受体激动剂，在临床手术中经常用作镇静麻醉剂，并且被认为在CIRI患者的预后中起关键作用。然而，DEX在CIRI中的潜在机制仍有待确定。本研究旨在探讨DEX对CIRI大鼠的神经保护作用。在治疗组中，在手术前30分钟腹腔注射DEX（50μg/kg）。采用大脑中动脉闭塞（MCAO）作为CIRI模型，大脑动脉闭塞2小时后再灌注24、72、120或168小时。通过Longa神经功能评分测试评估神经功能，结果显示MCAO组神经评分显著降低，梗死面积百分比增加，而DEX可阻止这种情况，表明DEX可能对治疗缺血性中风有效。在MCAO动物中，2,3,5-三苯基氯化四氮唑（TTC）显示出大面积明显的脑梗死区域，而DEX可使其面积减小。使用蛋白质印迹分析，结果显示在MCAO大鼠中，TNF-α和IL-6的蛋白质表达水平升高，同时PI3K/AKT信号通路的蛋白质表达水平降低。DEX预处理逆转了MCAO的影响，表现为TNF-α和IL-6的蛋白质表达水平降低，同时PI3K/AKT/NF-κB信号通路的蛋白质表达水平升高。数据表明，DEX预处理通过减轻炎症和激活PI3K/AKT/NF-κB信号通路，改善了MCAO后果动物的神经运动性能和认知功能。
