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sGC-cGMP信号通路在CO介导的呼吸节律调节中的作用

Role of sGC-cGMP Pathway in CO-mediated Regulation of Respiratory Rhythm
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摘要 目的探讨可溶性鸟苷酸环化酶(sGC)-环磷酸鸟苷(cGMP)信号通路是否参与一氧化碳(CO)在延髓水平介导的呼吸节律调节。方法电生理实验分为5组(每组n=8):单纯人工脑脊液(ACSF)对照组、外源性CO组、ODQ(sGC的选择性抑制剂)组、ODQ+CO组和二甲基亚砜(DMSO)组,制备SD大鼠离体延髓脑片标本,以舌下神经根节律性自发放电频率(burstfrequency,BF)为指标,分别灌流以上药物,观察呼吸节律的变化;并以放射免疫方法检测单纯ACSF对照组、外源性CO组、ODQ组和ODQ+CO组给药后脑片cGMP水平的改变(每组n=6)。结果外源性CO可以使BF减慢(P<0.05),cGMP水平升高(P<0.05)。ODQ使BF增快(P<0.05),cGMP水平降低(P<0.05)。在灌流ODQ的同时给予CO,BF和cGMP水平均无明显变化(P>0.05);给药结束后,BF增快(P<0.05)。结论在延髓水平,sGC-cGMP信号通路在CO介导的呼吸节律调控中具有重要作用。 Objective To identify the role of soluble guanylyl cyclase-cyclic guanine monophosphate (sGC- cGMP) pathway in the carbon monoxide (CO) mediating regulation of respiratory rhythm from the medulla oblongata. Methods Medullary slices of newborn Sprague-Dawley rats were prepared for the experiment. The electrophysiological experiment comprised 5 groups (each with 8 slices), each of which were perfused with artificial cerebrospinal fluid (ACSF control group), CO (exogenous CO group), 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (a specific inhibitor of sGC, ODQ group), ODQ +CO (ODQ +CO group), and dimethyl sulfoxide (vehicle of ODQ, DMSO group), respectively. The burst frequency (BF) of hypoglossal rootlets was recorded as an index of rhythmic respiratory activity. Radioimmunoassay was employed to determine cGMP levels of the medullary slices of the ACSF control group, exogenous CO group, ODQ group and ODQ+CO group (n= 6/ group). Results The exogenous CO decreased the BF (P〈0. 05) and increased the cGMP level (P〈0. 05). The ODQ increased the BF (P〈0. 05) and decreased the cGMP level (P〈0. 05). No significant changes were found in the BF and cGMP levels when CO and ODQ applied simultaneously (P〈0. 05), but the BF increased (P〈0.05) after the drug perfusion ended. Conclusion sGC-cGMP pathway may play an important role in the CO mediated regulation of respiratory rhythm from the medulla oblongata.
出处 《四川大学学报(医学版)》 CAS CSCD 北大核心 2007年第4期595-598,共4页 Journal of Sichuan University(Medical Sciences)
关键词 呼吸调节 一氧化碳 鸟苷酸环化酶 环磷酸鸟苷 延髓脑片 Respiratory regulation Carbon monoxide Guanylyl cyclase cGMP Medullary slice
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