尼可地尔对冠状动脉内皮细胞功能的影响  

Effect of nicorandil on the function of coronary artery endothelium during hypoxia reoxygenation

作　　者：李世康[1] 何立术[1] 周琦云[1] 胡应学[1] 冯志强[1] 孙宇[1] 

机构地区：[1]广西医科大学第一附属医院心胸外科,南宁530021

出　　处：《中华胸心血管外科杂志》2012年第8期492-493,499,共3页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：广西科学基金（桂科回0991007）

摘　　要：目的探讨尼可地尔对缺氧、复氧的冠状动脉内皮细胞功能的影响。方法新鲜猪心外膜下冠状动脉前降支中、下1／3部切3段，每段长2mm。取45段，单纯随机抽样法分5组，每组9段。各组冠状动脉血管环分别处理如下：对照组-未经缺氧、复氧处理，37~C有氧条件下Krebs—Henseleit（KH）液浸泡90min；A组-37℃、KH液缺氧浸泡30min后复氧30min；B组-37℃、KH液缺氧浸泡1h后复氧30min；C组- -37℃、含尼可地尔（0．1μmol／L）的KH液缺氧浸泡1h后复氧30min；D组-37℃、含尼可地尔（0．1μmoL／L）及5．羟基癸酸甘油酯（10μmol／L）的KH液缺氧浸泡1h后复氧30min。分别检测消炎痛（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和缓激肽引发的血管收缩、舒张反应。结果与对照组相比，缓激肽引发的血管环最大舒张反应，A、B、D组均明显降低（P〈0．001），c组变化不明显（P〉0．05）；与A组相比，B、D组明显降低（P〈0．001）。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，缺氧时间越长，损害作用越大。尼可地尔对其有保护作用，其机制可能与尼可地尔能选择性开放线粒体上的ATP敏感性钾离子通道有关。Objective To study the effect of nicorandil on the function of coronary artery endothelium during hypoxiareoxygenation. Methods Forty-five fresh porcine left anterior descending coronary artery rings in 2mm long were randomly divided into five groups. Control group （n = 9 ） ： incubation in Krebs-Henseleit （ KH ） at 37℃ for 90 minutes with a constant supply of oxygen; Group A （ n =9） ： 30-minute hypoxia （ PO2 〈 15 mm Hg） followed by 30 minutes reoxygenation in KH at 37℃ ; Group B （ n = 9 ） ： 60-minute hypoxia followed by 30 minutes reoxygenation in KH at 37℃; Group C （ n = 9 ） ： 60-minute hypoxia followed by 30 minutes reoxygenation in KH added nicorandil （ 0.2 μmol/L） at 37℃; Group D （ n = 9 ） ： 60-minute hypoxia followed by 30 minutes reoxygenation in KH added nicorandil （ 0.2 μmol/L ） and 5-hydroxydecanoate （ 10 μ mol/L） at 37℃. The endothelium-derived hyperpolarizing factor （EDHF） -mediated relaxation （ 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 was significantly decreased in group A, B and D （ P 〈 0. 001 ） , while there is no significant difference in group C （ P 〉 0.05 ）. Compared with group A, the relaxation was significantly reduced in group B and D （ P 〈0. 001 ）. Conclusion Hypoxia-reoxygenation impairs EDHF mediated relaxation in coronary artery with more injury during prolonged hypoxia. This function can be restored by preconditioning with nicorandil. The mechanism is mainly related to the mitochondrial ATP-sensitive K ＋ channels.

关 键 词：冠状血管 内皮 血管 内皮细胞 尼可地尔 

分 类 号：R965[医药卫生—药理学]