缺氧预处理对猪缺氧复氧冠状动脉内皮舒张功能的影响

The effect of hypoxic preconditioning on the function of coronary artery endothelium after hypoxia-reoxygenation

目的探讨缺氧预处理对猪缺氧复氧冠状动脉EDHF介导的内皮舒张功能的影响及其机制。方法随机选取新鲜猪心9个,每只取其心外膜下冠状动脉前降支中下1/3切成4段,长2mm,随机置入如下4组的环境中。对照组:冠脉血管环未经过缺氧/复氧处理,直接在37℃有氧条件下用KH液浸泡90min;实验组A:在4℃条件下用KH液缺氧浸泡60min后复氧30min;实验组B:先缺氧5min后复氧10min,再按实验组A的方法进行处理;实验组C:先用含5-羟基癸酸甘油酯(10μmol/L)的溶液浸泡25min,再按实验组B的方法进行处理。然后采用器官槽法检测血管环在消炎痛(7μmol/L)、N-硝基-L-精氨酸(300μmol/L)及氧合血红蛋白(20μmol/L)作用下,前列腺素F2α引发的血管收缩反应,及缓激肽引发的血管舒张反应。结果与对照组比较,缓激肽引发的血管环最大舒张反应,实验组A、C均明显降低(P<0.001),而实验组B变化不明显(P>0.05)。结论缺氧复氧会损害冠状动脉内皮源性超极化因子所介导的内皮依赖性舒张功能,缺氧预处理对其功能有保护作用。缺氧预处理能选择性开放线粒体ATP敏感的钾离子通道,可能是产生这一效果的主要原因。

Objective To study the effect of hypoxic preconditioning on the function of coronary artery endothelium after hypoxia-reoxygenation.Methods Thirty-six porcine coronary rings in 2 mm long were randomly divided into four groups.Control group（n=9）：incubation in Krebs-Henseleit（KH） at 37 ℃ for 90 minutes with a constant suply of oxygen;Group A（n=9）：60-minute hypoxia（PO2＆lt;15 mm Hg） followed by 30 minute reoxygenation in KH at 4 ℃;Group B（n=9）：hypoxia for 5 minutes followed by reoxygenation for 10 minutes before hypoxia-reoxygenation.Group C（n=9）：5-hydroxydecanoate（10 μmol/L） was given 20 miuntes prior to hypoxia preconditioning.The endothelium-derived hyperpolarizing factor（EDHF）-mediated relaxation（percentage of 30 nmol/L U46619 precontraction） induced by bradykinin in the present of indomethacin（7 μmol/L）,LNNA（300 μmol/L） and oxyhemoglobin（20 μmol/L） were measured in the organ chambers.Results Compared with control group,the relaxation induced by bradykinin was significantly decreased in group A,C,while there was no significant difference in group B.Conclusion Hypoxia-reoxygenation impairs EDHF mediated relaxation in coronary artery.This function can be restored by hypoxia preconditioning it′s effect might be related to mitochondrial ATP-sensitive K＋ channels.