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血竭对背根神经节神经元河豚毒素抗性钠电流的调节作用及其药效物质基础的鉴定

Modulation of dragon's blood on tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and identification of its material basis for efficacy.

作者信息

Liu Xiangming, Chen Su, Zhang Yuxia, Zhang Fan

机构信息

Department of Biological & Medical Engineering, South-Central University for Nationalities, Wuhan 430074, China.

出版信息

Sci China C Life Sci. 2006 Jun;49(3):274-85. doi: 10.1007/s11427-006-0274-4.

DOI:10.1007/s11427-006-0274-4
PMID:16856497
Abstract

To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.

摘要

为阐明血竭对背根神经节(DRG)神经元中河豚毒素抗性(TTX-R)钠电流的调节作用,并探索其相应的药效物质基础,采用全细胞膜片钳技术,观察了血竭及其提取的三种成分(原儿茶酸A、原儿茶酸B和龙血素B)对大鼠急性分离DRG神经元TTX-R钠电流的影响。根据所建立的中药药效物质基础的操作定义,从实验结果判断血竭对DRG神经元TTX-R钠电流调节的物质基础。采用Greco等人的药物相互作用方程评估血竭提取的三种成分的相互作用。本研究表明,血竭以剂量依赖的方式抑制TTX-R钠电流峰值,并影响TTX-R钠电流的激活。原儿茶酸A、原儿茶酸B和龙血素B联合使用的效果与血竭的效果一致。虽然三种成分单独使用时均可调节TTX-R钠电流,但在单独使用和联合使用对TTX-R钠电流抑制率相同时,单独使用三种成分的浓度分别高于联合使用时的浓度。三种成分的联合作用具有协同性。这些结果提示,血竭对DRG神经元TTX-R钠电流的调节所引起的对疼痛信息的干扰可能解释了血竭的部分镇痛作用,其相应的药效物质基础是原儿茶酸A、原儿茶酸B和龙血素B的组合。

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Ethanolic extract of Aconiti Brachypodi Radix attenuates nociceptive pain probably via inhibition of voltage-dependent Na⁺ channel.短柄乌头乙醇提取物可能通过抑制电压依赖性钠通道减轻伤害性疼痛。
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