中枢酸敏感离子通道对家兔呼吸活动调节的影响-复旦学报医学院版重点解读.docVIP

中枢酸敏感离子通道对家兔呼吸活动调节的影响 杨达伟1 张函1 陶雪飞1 陈珏伟1宋娜娜2沈霖霖2生理与病理生理学【】目的 观察中枢pH值改变对家兔呼吸活动调节的影响。方法 8只乌拉坦麻醉的成年家兔，记录膈神经放电信号，同时记录心电活动；一侧侧脑室微量注射不同pH的酸化人工脑脊液（pH=7.4、6.5、6.0、5.5、5.0、4.0，20μ）及酸敏感离子通道的阻断剂（Amiloride），NMDA受体激动剂（NMDA）和阻断剂（MK-801）。分析呼吸的频率、膈神经放电的积分面积和心率的改变。结果 （1）侧脑室微量注射不同pH 值的酸化脑脊液后，家兔呼吸频率显著增加，于pH 5.0达到最大效应，但在pH 4.0时呼吸频率的增加减弱。膈神经放电的积分面积与心率无明显变化。（2）侧脑室微量注射Amiloride后，酸化脑脊液引起家兔呼吸活动的兴奋作用减弱（P0.01, P0.05）。（3）侧脑室微量注射MK-801后，酸化脑脊液引起家兔呼吸活动的兴奋作用减弱，但没有统计学差异。微量注射NMDA后，酸化脑脊液引起家兔呼吸活动的兴奋作用增加（P0.05）。结论 家兔呼吸频率与侧脑室内pH值呈反向U型剂量关系，效应在pH 5.0时达顶峰。酸敏感离子通道的直接阻断剂Amiloride可以有效抑制酸化对呼吸中枢的兴奋作用，提示氢离子介导的呼吸中枢兴奋的调节机制与酸敏感离子通道有关。NMDA增加氢离子兴奋呼吸中枢的作用和NMDA受体阻断剂MK-801抑制氢离子兴奋呼吸中枢的作用，提示上游兴奋性氨基酸受体可能参与对酸敏感离子通道的调节。 【】酸敏感离子通道；酸化人工脑脊液；Amiloride；NMDA；MK-801；膈神经 【中图分类号】 Q473 【文献标识码】 A Effects of central acid sensing ion channels on modulation of respiratory activity in rabbits YANG Da-wei 1 ZHANG Han 1 TAO Xue-fei 1 CHEN Jue-wei 1 SONG Na-na 2 SHEN Lin-lin 2△ (1 Clinical Medicine; 2Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China) 【Abstract】 Present study investigated the effect of different pH artificial cerebrospinal fluid (ACSF) on modulation of respiratory activity in rabbits. Methods Experiment was performed on adult rabbits (n=8) with urethane anesthetized. The phrenic nerve discharge (PND) and electrocardiogram (ECG) were recorded simultaneously. Respiratory rate (RR) and integral value of PND were calculated from PND recording. Heart rate (HR) was calculated from ECG. Acidic ACSF (pH=7.4, 6.5, 6.0, 5.5, 5.0, 4.0, 20μl) and antagonist of ASICs or NMDA were microinjected into lateral ventricle (LV) in medulla. Results (1) Microinjection of acidic ACSF induced a rise in RR compared to normal saline without change of PND and HR. The response peak of RR was at pH 5.0. However it was less at pH 4.0 than at pH 5.0. (2) Amiloride, direct antagonist of ASICs, attenuated the RR response to acidic ACSF at pH 5.0 (P0.01, P0.05).