Department of Pharmacology, Ningxia Medical University, Yinchuan, China.
Planta Med. 2012 Jun;78(9):874-80. doi: 10.1055/s-0031-1298471. Epub 2012 Apr 24.
Our researches in recent years have shown that oxysophoridine (OSR), an alkaloid extracted from Siphocampylus verticillatus, presents antinociception through systemic and intracerebroventricular (icv) administration, and that OSR can also increase the GABA-immunopositive cells number in the central nervous system in rats. The purpose of the present study was to investigate the antinociception produced by OSR administered spinally, the interaction between OSR and GABAA receptor (GABAAR) agonists or antagonists on acute thermal nociceptive models (tail-flick test), and the possible alterations on the mRNA and protein expression of GABAAα1 receptors in the spinal cord. ICR mice were tested for their tail withdrawal response to thermal stimulation (tail-flick test). Quantitative real-time PCR and Western blot were used to inspect the influence of OSR administered by intrathecal injection (i. t.) on mRNA and protein expression of the GABAAα1 receptor in mice spinal cord by the formalin test. The experiments showed that OSR (0.13-0.25 mg/site, i. t.) significantly increased the tail withdrawal threshold with a peak effect of 68.35 % MPE at 20 min (p < 0.01). When OSR (0.06 mg/site, i. t.) was administered with gamma aminobutyric acid (GABA) (30.0 µg/site, icv) or muscimol (MUS) (0.10 µg/site, icv), the value of tail-flick latency was remarkably larger than with OSR alone (at 10 min, 45.67 % or 31.45 %, p < 0.01). Picrotoxin (PTX) and bicuculine (BIC) can significantly antagonize the antinociception of OSR. OSR (0.25 mg/site, i. t.) can increase the expression of mRNA and protein of the GABAAα1 receptor in the spinal cord (L5-L6). The results reveal that i. t. administered OSR presents effective antinociception whose action is mainly located in the spinal cord. The antinociception of OSR results from the activation of the GABAA receptor and from the regulation of the GABAAα1 receptor-mediated neurotransmission.
近年来的研究表明，从垂序商陆中提取的氧化苦参碱（OSR）通过全身和脑室内（icv）给药具有抗伤害感受作用，并且 OSR 还可以增加大鼠中枢神经系统中 GABA 免疫阳性细胞的数量。本研究的目的是研究 OSR 椎管内给药产生的抗伤害感受作用，OSR 与 GABA A 受体（GABAAR）激动剂或拮抗剂在急性热伤害感受模型（尾巴闪烁试验）上的相互作用，以及 OSR 对脊髓中 GABA Aα1 受体的 mRNA 和蛋白表达的可能改变。我们用热刺激（尾巴闪烁试验）测试 ICR 小鼠的尾巴退缩反应。通过福尔马林试验，用定量实时 PCR 和 Western blot 检测鞘内注射（i.t.）OSR 对小鼠脊髓中 GABA Aα1 受体 mRNA 和蛋白表达的影响。实验表明，OSR（0.13-0.25 mg/site，i.t.）可显著增加尾巴退缩阈值，在 20 分钟时达到 68.35%的最大效应（p < 0.01）。当 OSR（0.06 mg/site，i.t.）与γ-氨基丁酸（GABA）（30.0 µg/site，icv）或 muscimol（MUS）（0.10 µg/site，icv）一起给药时，尾巴闪烁潜伏期的值明显大于单独使用 OSR（在 10 分钟时，45.67%或 31.45%，p < 0.01）。荷包牡丹碱（PTX）和印防己毒素（BIC）可显著拮抗 OSR 的抗伤害感受作用。OSR（0.25 mg/site，i.t.）可增加脊髓（L5-L6）中 GABA Aα1 受体的 mRNA 和蛋白表达。结果表明，椎管内给予 OSR 可产生有效的抗伤害感受作用，其作用主要位于脊髓。OSR 的抗伤害感受作用源于 GABA A 受体的激活和 GABA Aα1 受体介导的神经传递的调节。
