Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that exerts sympatholytic effects in specific brain regions, providing analgesic, sedative, and anxiolytic actions[1-2]. In addition, Dexmedetomidine preconditioning effectively shields the heart against ischemia-reperfusion injury[3].
In vitro, after 3 days of treatment with graded Dexmedetomidine concentrations (0.05μM, 0.1μM, 1μM, 2.5μM, 5μM, or 10μM), cortical neurons showed unchanged viability below 10μM but a significant drop in viability and increased cell death at 10μM[4]. Exposure of PC12 cells to Dexmedetomidine at 50ng/ml, 200ng/ml, or 800ng/ml for 12 or 24h enhanced cell viability in both a time- and dose-dependent manner[5].
In vivo, in acute liver injury (ALI) C57BL/6 mice, a single intraperitoneal dose of Dexmedetomidine (200mg/kg) markedly blunted the rises in ALT and AST and suppressed the ALI-induced elevations of serum IL-6, IL-8, IL-1β, and TNF-α[6]. In male C57BL/6 mice, a single intraperitoneal dose of Dexmedetomidine (40μg/kg) suppresses lipopolysaccharide (LPS)-induced inflammatory factor expression and protects renal cells from apoptosis[7]. Administering Dexmedetomidine (10 or 20μg/kg; i.p.) to Sprague-Dawley rats dose-dependently reduces mortality and suppresses pulmonary inflammation by inhibiting the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/NF-κB pathway[8].
References:
[1] Hou M, Chen F, He Y, et al. Dexmedetomidine against intestinal ischemia/reperfusion injury: A systematic review and meta-analysis of preclinical studies. Eur J Pharmacol. 2023;959:176090.
[2] Dardalas I, Stamoula E, Rigopoulos P, et al. Dexmedetomidine effects in different experimental sepsis in vivo models. Eur J Pharmacol. 2019;856:172401.
[3] Takahashi K, Yoshikawa Y, Kanda M, et al. Dexmedetomidine as a cardioprotective drug: a narrative review. J Anesth. 2023;37(6):961-970.
[4] Jimenez-Tellez N, Iqbal F, Pehar M, et al. Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model. Sci Rep. 2021;11(1):16153.
[5] Guo Q, Ma M, Yu H, et al. Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1. Ann Med. 2023;55(1):2209735.
[6] Zhang C, Fan Y, Qin Z, et al. Network pharmacology and experimental validation reveal dexmedetomidine's protective mechanisms against acute liver injury in mice. Sci Rep. 2025;15(1):9044.
[7] Kang K, Gao Y, Wang SC, et al. Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an α7 nAChR-dependent pathway. Biomed Pharmacother. 2018;106:210-216.
[8] Wu Y, Liu Y, Huang H, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway. Mediators Inflamm. 2013;2013:562154.
Dexmedetomidine是一种高选择性α2-肾上腺素能受体激动剂，可在脑内特定区域发挥交感神经抑制作用，具有镇痛、镇静和抗焦虑效应[1-2]。此外，Dexmedetomidine预处理可有效保护心脏免受缺血-再灌注损伤[3]。
在体外，经0.05、0.1、1、2.5、5或10μM梯度浓度Dexmedetomidine处理3天后，皮层神经元在10μM以下活力无明显变化，而10μM时活力显著下降并出现细胞死亡增加[4]。用50、200或800ng/ml的Dexmedetomidine处理PC12细胞12或24小时，可在时间和剂量依赖性方式下提高细胞活力[5]。
在体内，在急性肝损伤（ALI）C57BL/6小鼠中，单次腹腔注射200mg/kg的Dexmedetomidine可显著降低ALT和AST的升高，并抑制ALI诱导的血清IL-6、IL-8、IL-1β和TNF-α水平[6]。在雄性C57BL/6小鼠中，单次腹腔注射40μg/kg的Dexmedetomidine可抑制脂多糖（LPS）诱导的炎症因子表达并保护肾细胞免于凋亡[7]。对Sprague-Dawley大鼠腹腔给予10或20μg/kg的Dexmedetomidine可剂量依赖性地降低死亡率，并通过抑制Toll样受体4（TLR4）/髓样分化因子88（MyD88）/NF-κB通路减轻肺部炎症[8]。