不同频率间歇低氧暴露后兔颈动脉体的炎症状态和窦神经传入活性  

Carotid body inflammation and carotid sinus nerve afferent activity after intermittent hypoxia exposure of various frequencies in rabbits

作　　者：冯靖[1] 陈宝元[1] 崔林阳[2] 王宝利[3] 刘春霞[1] 陈攀峰[1] 郭美南[1] 董丽霞[1] 李硕[1] 

机构地区：[1]天津医科大学总医院呼吸科,300052 [2]天津市神经病学研究所 [3]天津医科大学代谢病医院内分泌学研究所

出　　处：《中华结核和呼吸杂志》2008年第9期670-674,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的建立不同间歇低氧／再氧合（IH／ROX）模式家兔颈动脉体在体模型，探讨不同频率IH／ROX暴露后家兔颈动脉体的炎症状态、内皮素水平和颈动脉体窦神经传入活性。方法49只成年雄性大耳白家兔（2．5～3．0kg）分为7组，每组7只，分离右侧颈总动脉和右窦神经，窦神经去包膜显露髓鞘，游离化学感受性神经细束记录窦神经传入活性。结扎近心端，远心端内插入导管，经程控蠕动泵交替灌注以发泡法预平衡的低氧灌注液和（或）正常氧灌注液，在右侧颈总动脉内模拟睡眠呼吸暂停模式IH／ROX暴露条件或持续低氧条件。按灌注频率分组为：间歇正常氧组（21％O2，15S；21％O2，1min45S）、10次／h组（21％O2，5min45S）、30次／h组（21％02，1min45S）、50次／h组（21％O2，57s）、60次／h组（21％O2，45s）、90次／h组（21％O2，25S），均反复灌注60次；持续低氧组：间歇正常灌注1h45min，随后给予5％O2持续15min。静置30min，采集窦神经传入活性频率（ChargeF），游离收集右侧颈动脉体，酶联免疫吸附法（ELISA法）测定颈动脉体裂解液中白细胞介素-6（IL-6）、内皮素-1、低氧诱导因子-1（HIF-1）和血管内皮生长因子（VEGF）浓度并标准化。整体比较时采用单因素方差分析，配对比较用TamhaneT2法。结果随着间歇正常氧频率增加，IL-6、内皮素-1和ChargeF整体均数呈现出先升后降趋势（F=25601．39，2390．48，6945．84，均P〈0．05），50／hr组IL-6、内皮素-1和ChargeF水平均高于其余各组。且ChargeF与IL-6和内皮素-1相关（r=0．736，0．757，均P〈0．05）；而组间IL-6、内皮素-1和ChargeF水平差异不明显。随着间歇低氧频率增加，HIF-1水平逐渐增加（F=5241．10，P〈0．01），持续低氧组HIF-1水平最高。VEGF水平呈现出先升后降再升趋势（F=5931．30，P〈0．05），持续低氧组VEGF水平增加最明显。�Objective To explore the inflammatory reactions, endothelin level and carotid sinus nerve （CSN） afferent activity of carotid body （CB） after intermittent hypoxia/reoxygenation （IH/ROX） exposure of various frequencies in rabbits. Methods Forty-nine male adult New Zealand white rabbits （2. 5 - 3.0 kg） were separated into 7 groups （ n = 7 each）. After anesthetization, the right carotid artery and CSN were cleared of surrounding tissues without touching the right CB and the left carotid region. The CSN was unenveloped to partially expose the myelin sheath, and electrodes were placed to the ＂ single＂ chemoreceptor bundle of the CSN, with CSN afferent activity carefully monitored and recorded. Then the fight common carotid artery was exposed, cannulated to distal part and its proximal part was ligated. Preparations were challenged by changing the PO2 of the gas mixture equilibrating the perfusate. Alternatively perfusion （2 ml/min） of equilibrated perfusate bubbled with normoxia or hypoxia gas mixtures formed IH/ROX cycles in right carotid common artery, simulating the pattern of hypoxic episodes seen in obstructive sleep apnea, or with continuously perfusing hypoxia perfusate to form continuous hypoxia （CH） modes. Groups were defined with different frequencies, and groups were： intermittent normoxia group （IN group） （21%O2,15 s;21%O2,1 min 45 s）, 10/hr group （5%O2,15 s;21%O2,5 min45 s）, 30/hr group （5%O2,15 s;21%O2,1 min45 s）, 50/hr group （5%O2,15 s;21%O2,57 s）, 60/hr group （5% O2,15 s ;21% O2 ,45 s） and 90/hr group （5% O2,15 s ;21% O2 ,25 s）. All the above groups were exposed to 60 treatment cycles; continuous hypoxia group （ CH group）, IN for 1 h 45rain and then 5% O2 for 15 min. After exposure and 30 min of static placing, CSN afferent frequencies （Charge F） were recorded from chemoreceptor bundles, and the right CB was cleared of surrounding tissues and harvested. Interleukin-6 （IL-6） , endothelin-1 （ET-1）, hypoxia-indueible factor-1 （

关 键 词：缺氧 颈动脉体 颈动脉窦 交感神经系统 高血压 

分 类 号：R686[医药卫生—骨科学]