Dexmedetomidine, a selective α₂ adrenergic agonist, has been shown to have neuroprotective and anti-apoptotic effects. To further investigate the underlying mechanisms, we used a rat model of spinal neurotoxicity induced by intrathecal administration of lidocaine. Four days after intrathecal catheter implantation, rats received an intraperitoneal injection of various doses of dexmedetomidine before an intrathecal injection of 20 μL 10% lidocaine. Dexmedetomidine-pretreated rats were also exposed to a selective α₂-adrenergic antagonist (yohimbine) or a specific protein kinase C (PKC) inhibitor (Gö 6983) that selectively inhibits several PKC isoforms. Lidocaine injection significantly damaged the spinal cord: hind limb locomotor function was reduced and tail-flick latency was prolonged; significant spinal cord damage and neuronal apoptosis were identified using histological and TUNEL staining assays; increased glutamate release was detected using high performance liquid chromatography (HPLC) analysis; and increased expression of PKC and PKCβI was detected using Western blotting analysis. Pretreatment with dexmedetomidine ameliorated all of the lidocaine-induced effects; however, this protection was abolished when yohimbine or Gö 6983 was injected together with dexmedetomidine. Our results indicate that dexmedetomidine protects the spinal cord from lidocaine-induced spinal neurotoxicity through regulating PKC expression and glutamate release.

右美托咪，选择性α ₂肾上腺素能受体激动剂，已经显示出具有神经保护和抗凋亡作用。为了进一步研究其潜在机制，我们使用了鞘内注射利多卡因诱导的大鼠脊髓神经毒性模型。鞘内导管植入后四天，大鼠在鞘内注射20μL10％利多卡因之前接受腹膜内注射各种剂量的右美托咪定。右旋美托咪预处理大鼠也暴露于选择性α ₂-肾上腺素拮抗剂（育亨宾）或特定的蛋白激酶C（PKC）抑制剂（Gö6983），可选择性抑制几种PKC亚型。注射利多卡因会严重损害脊髓：后肢运动功能降低，甩尾潜伏期延长；使用组织学和TUNEL染色法鉴定出明显的脊髓损伤和神经元凋亡；使用高效液相色谱（HPLC）分析检测到谷氨酸盐释放增加；Western blotting检测发现PKC和PKCβI表达增加。右美托咪定预处理可改善所有利多卡因诱导的作用；但是，将育亨宾或Gö6983与右美托咪定一起注射时，这种保护作用被取消。