选择性钠氢通道拮抗剂HOE642对未成熟心肌的保护作用  

Cardioprotective effects of selective Na^＋/H^＋ exchanger inhibitor HOE642 against ischemia/reperfusion injury in immature hearts

作　　者：周荣华[1] 刘斌[2] 刘进[2] 关彬[1] 张艳婉[1] 高国栋[1] 史世勇[1] 温福兴[1] 龙村[1] 

机构地区：[1]中国医学科学院阜外心血管病医院体外循环科,北京100037 [2]四川大学华西医院麻醉科

出　　处：《中华实验外科杂志》2007年第3期268-270,共3页Chinese Journal of Experimental Surgery

摘　　要：目的比较选择性钠氢通道（NHE1）拮抗剂HOE642在缺血／再灌注不同阶段（缺血前、缺血中、再灌注期）对未成熟心肌的保护作用。方法建立Langendorff离体心脏灌注模型，32只新西兰幼兔随机分为对照组（组Ⅰ，n=8）和HOE642治疗组（n=24），根据给药时间不同，HOE642治疗组又分为：组Ⅱ（n=8）、组Ⅲ（n=8）和组Ⅳ（n=8）。所有心脏均37℃全心缺血60min。再灌注60min。组Ⅱ心脏停跳前采用HOE642预处理15min；组Ⅲ在St，Thomas停跳液中加入HOE642；组Ⅳ于再灌注最初15min内的KH缓冲液中加入HOE642。测定再灌注期左室发展压（LVDP）、最大收缩变化率（＋dp／dtmax）、最大舒张变化率（～dp／dtmax）及冠脉流量（CAF）；测定心肌细胞内三磷酸腺苷（ATP）、丙二醛（MDA）及心肌含水量（WC）；并用透射电镜观察心肌细胞超微结构改变。结果HOE642各治疗组LVDP、＋dp／dtmax／dp／dtmax、CAF恢复率及ATP含量明显高于对照组（P〈0．05），MDA、心肌含水量明显低于对照组（P〈0.05）。HOE642治疗组之间，组Ⅳ再灌注前15min时＋dp／dtmax、-dp／dt。恢复率低于组Ⅱ和组Ⅲ（P〈0.05），而60min时CAF恢复率高于组Ⅱ和组Ⅲ（P〈0.05）；组ⅡATP高于组Ⅲ和组Ⅳ（P〈0.05），其余指标差异无统计学意义（P〉0．05）。超微结构显示，HOE642治疗能减轻心肌细胞损伤；而HOE642治疗组间，组Ⅳ损伤程度重于组Ⅱ和组Ⅲ。结论缺血／再灌注不同阶段使用HOE642都能减轻未成熟心肌缺血再灌注损伤，而缺血前使用更利于心脏功能恢复、减少心肌损伤。Objective To compare the cardioprotective effect of HOE642, a highly selective Na^＋/H ^＋ exchanger isoform-1 （NHEI） inhibitor, administered at different phase of ischemia/reperfusion in immature hearts：pre-ischemia, during ischemia and reperfusion. Methods Thirty-two isolated immature rabbit hearts were randomly divided into two groups ： the control group （ group Ⅰ , n = 8 ） and the HOE642 treated group （n = 24）, when equilibrated on the Langendorff apparatus. According to the phases of the drug administration, HOE642 treated group was divided into 3 sub-groups ： group Ⅱ （ n = 8 ）, group m （ n = 8 ）, and group Ⅳ （ n = 8 ）. All hearts were arrested with St. Thomas cardioplegia before sobjected to 60 min normothermic global ischemia plus 60 min reperfusion （I/R）. In group Ⅱ ,hearts were pretreated with HOE642 for 15 min before I/R. In group Ⅲ ,HOE642 was added to St. Thomas eardioplegia. In group Ⅳ ,hearts were perfused with HOE642 during the first 15 min of reperfusion. Myocardial function variables （LVDP, ＋ dp/dtmax, -dp/dtmax ）, coronory artery flow （CAF）, ATP, MDA and myocardial water content （WC） were measured. Myocardial uhrastructure was observed under transmission electron microscopy. Results Recoveries of most myocardial function variables, LVDP, ＋ dp/dtmax, - dp/dtmax, and CAF, in HOE642 treated groups were markedly higher than in control group （P 〈 0.05 ）. Moreover, HOE642 significantly reduced MDA and water content, increased ATP reserve （P 〈 0.05）. Among treatment groups, LVDP, ＋ dp/dtmax, - dp/dtmax ,CAF recovery in the first 15 min of reperfusion were higher in groups Ⅱ , Ⅲ than in group Ⅳ（ P 〈 0.05）. ATP was higher in group Ⅱ than in the other two HOE642 treated groups （ P 〈 0.05 ）. There were no signifcant differences in other indexes among the HOE642 treated groups （ P 〉0.05）. The ultrastructural assessment under transmission electron microscopy revealed that HOE642 produced obvious myocyte sa

关 键 词：心肌 缺血 再灌注损伤 钠氢通道 HOE642 

分 类 号：R686[医药卫生—骨科学]