Evaluation of chemical mediator-induced respiratory center inhibition in medulla

化学介质诱导延髓呼吸中枢抑制的评价

• 批准号: 12671506
• 负责人: TAKEDA Shinhiro
• 金额: $ 1.86万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671506/
• 关键词: medulla; respiratory center; respiratory neuron; サイトカイン

Membrane potential and resistance (Rm) were measured in inspiratory neurons in rostral ventrolateral medulla (RVLM) of the isolated brainstem - spinal cord preparation from newborn rats during bath application of opioids (μ-,κ-, and δ- receptor agonists), cytokine (TNF-alfa), and NSAID (salicylate).μ-andκ-opioid receptor agonists caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be due to both a pre - and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists.TNF-alfa induced respiratory depression. Resting membrane potential hyperpolarized and Rm decreased. These results mean that TNF-alfa-induced respiratory depression seems to be a postsynaptic action.Low dose salicylate increased in inspiratory neuron burst. While the burst rates of inspiratory neuron were decreased after application of high dose salicylate. While the depressant effects by 10 mM salicylate were antagonized by GABA receptor antagonist. Resting membrane potential did not change. Salicylate effects on the medullary inspiratory neurons seem to be due to presynaptic effect. GABAergic mechanisms are probably involved in the salicylate-induced central respiratory depression.

在新生大鼠离体脑干-脊髓标本上，应用阿片类药物（μ-、κ-和δ-受体激动剂）、细胞因子（TNF-α）和NSAID（水杨酸盐），测定了延髓头端腹外侧区（RVLM）吸气神经元的膜电位和电阻（Rm）。μ-和κ-阿片受体激动剂主要通过抑制延髓吸气神经元网络，引起最终运动输出减少。吸气神经元的这种抑制似乎是由于突触前和突触后抑制。由吸气前神经元爆发率反映的中枢呼吸节律基本上不受激动剂的影响。TNF-α诱导呼吸抑制。静息膜电位超极化，Rm降低。这些结果表明TNF-α诱导的呼吸抑制可能是一种突触后作用，低剂量水杨酸可增加吸气神经元的爆发性放电。而高剂量水杨酸可降低吸气神经元的爆发频率。GABA受体拮抗剂可拮抗10 mM水杨酸的抑制作用。静息膜电位无变化。水杨酸对延髓吸气神经元的作用可能是通过突触前作用实现的。GABA能机制可能参与水杨酸诱导的中枢呼吸抑制。

项目成果

Takeda S. et al.: "Opioid action on respiratory neuron activity of the isolated respiratory network in newborn rats"Anesthesiology. 95. 740-749 (2001)

Takeda S. 等人：“阿片类药物对新生大鼠离体呼吸网络的呼吸神经元活动的作用”麻醉学。

Takeda S. et al.: "Opioid action on respiratory neuron activity of the isolated respiratory network in newborn rats"Anesthesiology. 95・3. 740-749 (2001)

Takeda S.等人：“阿片类药物对新生大鼠离体呼吸网络的呼吸神经元活动的作用”麻醉学95・3（2001）。

Takeda S, et al.: "Opioid action on respiratory neuron activity of the isolated respiratory network in newborn rats"Anesthesiology. 95. 740-749 (2001)

Takeda S 等人：“阿片类药物对新生大鼠离体呼吸网络呼吸神经元活动的作用”麻醉学。