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大鼠海马对呼吸的调控及Ca~(2+)对阿片类物质呼吸抑制作用的影响

The Regulation of Respiration in Rat by Hippocampus and the Effects of Ca~(2+) on the Respiratory Inhibition Induced by Opioids

【作者】 朱国运

【导师】 金荫昌;

【作者基本信息】 中国协和医科大学 , 药理学, 1993, 博士

【摘要】 本文以大鼠为研究对象,用电刺激和微量注射方法观察海马及阿片类物质对呼吸的调节作用;用计算机实时监测方法及微电极记录方法观察钙及钙通道阻断荆对阿片类物质呼吸抑制效应的影响;用Fura-2荧光测定技术观察不同阿片受点激动剂对[Ca2+]i的影响。主要结果如下: 一、电刺激及化学刺激海马对大鼠膈神经放电的影响 电刺激海马腹部对大鼠膈神经放电表现出兴奋或抑制效应。在所刺激的80个位点中,有28个刺激点表现为抑制效应;抑制率为22.2±2.6%。抑制效应点主要位于尾端腹侧;有38个点表现为兴奋效应,膈神经放电频率增加22.8±2.8%。兴奋位点主要位于头端背侧。有部分兴奋、抑制位点交叉。停止刺激后,作用仍可维持30s左右。结果表明海马对呼吸的调节作用。 海马内注射谷氨酸钠后(2μmol),膈神经放电频率明显增加,与给药前相比最高达35.7±22%。给药后20min兴奋作用达最大,以后逐渐恢复正常。表明谷氨酸对呼吸有兴奋作用。 海马内注射Mor(10μg)、OMF(0.1μg),膈神经放电频率明显降低。给药后迅速出现抑制效应,分别于30min,20min达最大,最大抑制率分别为66.7±9.0%,74.9±4.8%。海马内注射U50488(50μg),膈神经放电频率减慢,给药后5min出现抑制效应,20min后达最大,为41.0±6.9%。海马内注射纳洛酮(20μg),给药前后膈神

【Abstract】 The present study regards: (1) a role of hippocampus on the respiratory regulation in rat and its response to microinjected opioids; (2) the modulation of opioids -induced respiratory inhibition by Ca2+ and calcium channel antagonists; (3) the effects of Ca2+ on the inhibitory effect of opioids on the spontaneous and induced discharges of respiratory neurones in nucleus ambiguus; and (4) the effects of opioid receptor agonists on intracellular free calcium. The results are as follows:1. Respiratory changes induced by electircal and chemical stimulation of ventral hippocampusElectrical (15 s trains of 0.25 ms pulses at 50 Hz, 4 V) stimulation at the ventral hippocampus evoked inhibitory, facilitatory, or altering effects in phrenic nerve discharges. In the 80 points stimulated, 28 of which showed depression were located mainly in the caudal ventral hippocampus. Phrenic nerve discharges decreased 22.2±2.6%. The 38 points which showed excitation were found in

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