吡咯二硫氨基甲酸酯联合超极化停搏液对兔离体心脏缺血再灌注损伤的保护作用  

Protective effect of hyperpolarized cardioplegia in combination with pyrroline dithiocarbamate on myocardium against ischemia-reperfusion injury to isolated rabbit hearts

作　　者：王海英[1] 喻田[1] 刘兴奎[1] 余志豪[1] 黄燕[1] 

机构地区：[1]遵义医学院麻醉学系,遵义市563003

出　　处：《中华麻醉学杂志》2005年第5期351-355,共5页Chinese Journal of Anesthesiology

基　　金：贵州省优秀青年人才培养基金(2002-0217)

摘　　要：目的观察吡咯二硫氨基甲酸酯(PDTC)联合超极化停搏液对兔离体心脏缺血再灌注损伤的保护作用。方法日本大耳白兔112只,其中96只随机分为6组,分别为:空白对照组(K组);St.TbomasⅡ组(S组);吡那地尔组(P组);PDTC联合K-H液组(PK组);PDTC联合St.ThomasⅡ组(PS组);PDTC联合含吡那地尔的停搏液组(PP组),后三组在取兔心脏前10min静脉注射PDTC15mg·kg-1,而前三组注射等量生理盐水,每组16只。剩余16只作为正常组,在灌注K-H液平衡10min后取心肌组织,进行免疫组化检测。各组离体心脏Langendorff模型平衡灌注充氧K-H液10min后(平衡10min),按分组灌注停跳液。全心缺血40min,每组中8只复灌60min,8只复灌120min。记录从复灌开始至心脏开始跳动的时间(TR);分别于平衡10min、复灌15、30、60、120min时记录心率(HR)、左室收缩压(LVSP)、左室内压最大上升速率(+dp/dtmax)的恢复率及左室舒张末压(LVEDP);于平衡10min、复灌60min时测定冠状静脉流出液中肿瘤坏死因子-α(TNF-α)浓度;于平衡10min、复灌60、120min时测定心肌NF-κBp65阳性率;于平衡10min、复灌120min时测定心肌细胞粘附分子-1(ICAM-1)表达。结果与其它各组比较,P、PS、PP组心脏TR均缩短,PP组在复灌15-120min时HR、LVSP、+dp/dtmax时恢复率升高,LVEDP降低(P<0.05或0.01);与K、S、P组比较,PK、PS、PP组在复灌60min时冠状静脉流出液TNF-α浓度降低(P<0.01);PK、PS、PP组复灌60、120min时心肌NF-κBp65阳性率、复灌120min时心肌。ICAM-1表达均低于K、S、P组(P<0.05或0.01)。结论超极化停搏液联合PDTC能较好地保护心肌缺血再灌注损伤,其保护作用强于单纯用超极化停液、去极化停搏液、去极化停搏液联合PDTC。Objective To evaluate the myocardial protective effects of pinacidil combined with pyrrolidine dithiocarbamate (PDTC) against ischemia-reperfusion (I/R) injury to the isolated rabbit hearts and investigate its mechanisms. Methods One-hundred and twelve Japanese long-ear white rabbits of both sexes weighing 1.8-8.2 kg were killed by a knock to the head after heparinization. Their hearts were immediately removed and mounted on Langendorff apparatus and perfused with oxygenated K-H solution at 371 . Of the 112 isolated hearts 96 were randomized into 6 groups with 16 hearts in each group of which 8 hearts underwent 60 min reperfusion and another 8 hearts 120min reperfusion after 40min global myocardial ischemia: the hearts were perfused with K-H solution in group Ⅰ(K); with St Thomas Ⅱ solution in group Ⅱ(S); with pinacidil in group Ⅲ(P); with PDTC + K-H solution in group Ⅳ(PK); with PDTC + St Thomas Ⅱ solution in group Ⅴ(PS) and with PDTC + pinacidil in group Ⅵ(PP) . The rest of the 112 hearts (16 hearts) were perfused with K-H solution for 10 min. Then myocardial tissue was obtained for immuno-histochemical examination (SABC staining) used as normal control value.(1) Time of resumption of heart beat (from the beginning of reperfusion to the resumption of heart beat) was recorded; (2) left ventricular systolic and end-diastolic pressure (LVSP, LVEDP) and + dp/dtmax were monitored; (3) effluent from coronary sinus was collected at 60 min of reperfusion for determination of TNF-α concentration and (4) myocardial tissue was obtained at the end of reperfusion for determination of expression of NF-κB p65 and ICAM-1 in myocardium. Results (1) The heart beat resumption time was significantly shorter in group PP, PS and P than in the other 3 groups (P < 0.01). (2) The recovery of HR, LVSP and + dp/dtmax, at 15-120 min of reperfusion as compared with the baseline values before I/R were significantly better and LVEDP was significantly lower in group PP than in the other 5 groups (P < 0.01 or 0.05). (3) The T

关 键 词：心脏缺血再灌注损伤 超极化停搏液 保护作用 吡咯二硫氨基甲酸酯(PDTC) 肿瘤坏死因子-α(TNF-α) Langendorff模型 ST.THOMAS 心肌缺血再灌注损伤 ICAM-1表达 TNF-Α浓度 NF-κB 日本大耳白兔 免疫组化检测 心率(HR) 左室舒张末压 

分 类 号：R541[医药卫生—心血管疾病]