选择性钠-氢离子交换抑制剂预处理对未成熟心肌保护作用.docVIP

选择性钠/氢离子交换抑制剂预处理对未成熟心肌保护作用 　 作者：周荣华 ，刘斌，刘进，关彬，张艳婉，史世勇，温福兴，龙村 【关键词】 缺血再灌注损伤 摘要：目的 研究选择性Na+/H+ 交换抑制剂HOE642（Cariporide）预处理对未成熟心肌缺血/再灌注损伤的保护作用及机制。方法 20只健康新西兰幼兔（3~4周龄），利用Langendorff左室做功模型灌注其离体心脏,建立全心缺血/再灌注模型。KH液自主动脉逆行灌注心脏，向球囊缓慢注入生理盐水，调整至左室舒张末压（LVEDP）为10mmHg, 做功20 min，随机分为两组，组Ⅰ: 对照组，继续灌注15min；组Ⅱ：HOE642预处理组，用加入HOE642的KH液（浓度为5μmol/L）继续灌注15min。然后两组心脏均以St.Thomas停搏液诱导停跳，常温（37℃）缺血45min（保湿保温），再灌注60 min。记录冠脉流量（CAF），多导生理记录仪记录左心功能指标， 原子吸收分光光度计测定心肌细胞内钙（Ca）含量,自动生化分析仪测量冠脉流出液中磷酸肌酸激酶（CK）、磷酸肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）漏出量含量，计算心肌含水量，透射电镜观察心肌超微结构改变。结果 CAF、左室发展压（LVDP）、左室压力微分（±dp/dtmax）恢复率，心肌组织内Ca 及心肌含水量，心肌超微结构变化，HOE642预处理组明显优于对照组（Plt;0.05）。结论 HOE642预处理通过减少细胞内钙超载，模拟缺血预处理的心肌保护效果，对未成熟心肌缺血/再灌注损伤有明显的保护作用。 　　关键词：Na+/H+ 交换;预处理;未成熟心肌;缺血再灌注损伤;钙超载 　　Selective Na+/H+ Exchanger Inhibitor HOE642 Preconditioning Exihibits Markedly Protective Effect on Immature Rabbit Hearts 　　　Abstract: OBJECTIVE To investigate the protective effect of HOE642 Preconditioning against ischemia-reperfusion injury on immature myocardium and its mechanisms.METHODS The Langendorff perfused isolated working immature rabbit heart model was established. After perfused by Krebs-Henseleit buffer solusion bubbled with 95%O2~5%CO2 gas mixture at 70cmH2O for 20min, 20 isolated hearts of New Zealand healthy white immature rabbits (3~4 weeks old ,weighing 300g~350g) were randomly divided into 2 groups:the groupⅠ:the control group(n=10)；groupⅡ:HOE642 preconditioning group(n=10). In group Ⅰ,the hearts were perfused for 15min by Krebs-Henseleit buffer;In group Ⅱ, HOE642(5μmol/L)was added to Krebs-Henseleit buffer and the hearts were perfused for 15min .Then St.Thomas solution was used ,and all hearts were subjected to 45min global ischemia and 60min reperfusion. Perfusate temperature and ischemic heart temperature were both maintained at 37℃. Myocardial calcium content was examined . Hemodynamics　variables(LVDP, ±dp/dt),myocardial water content(WC), coronory artery flow (CAF),leakage of myocardial enzyme(CK,CK-MB,LDH)were also calculated. My