摘要
目的探讨促红细胞生成素（EP0）对窒息性心搏骤停大鼠心肺复苏（cPR）后心功能不全的心肌保护作用。方法经夹闭气管8min建立窒息性心搏骤停一CPR动物模型。按随机数字表法将24只SD大鼠分为3组，每组8只。CPR组窒息致心搏骤停后8min予胸外按压和机械通气进行复苏；EP0组于自主循环恢复（ROSC）后3min股静脉注射EP05kU／kg；正常对照组不予任何处理。持续监测左心室收缩压（LVSP）、左心室舒张期末压（LVEDP）、左心室内压上升或下降最大速率（＋dp／dtmax）等血流动力学指标。于观察终点（ROSC后120min）处死大鼠，采血测定血清心肌肌钙蛋白I（cTnI）含量；光镜和透射电镜下观察心肌组织病理改变；原位末端缺刻标记法（TUNEL）检测心肌细胞凋亡。结果CPR组和EPO组ROSC后30、60、90、120min时LVSP、＋dp／dtmax和-dp／dtmax绝对值均较基线水平明显下降。与正常对照组比较，CPR组和EPO组ROSC30min时LVSP（mmHg，1mmHg=0．133kPa）、＋dp／dtmax（mmHg／s）、dp／dtmax绝对值（mmHg／s）即明显下降（LVSP：119．52±12．68、134．32±15．78比165．82±7．05；＋dp／dtmax：4457．14±826．22、6019．85±1192．19比10325．93±773．09；-dp／dtmax：-3956．04±952．37、4957．22±838．60比8421．33±886．65，均P〈0．01），并持续至ROSc120min（LVSP：124．62±8．07、145．61±16．70比162．34±7．63；＋dp／dtmax：4977．67±350．40、7471．62±998．32比9999．39±727．96；-dp／dtmax：-4145．51±729．77、-5895．64±787．30比-8089．75±981．52，均P〈0．01）；经EPO处理后ROSC各时间点LVSP、＋dp／dtmax和-dp／dtmax绝对值均较CPR组显著升高（均P〈0．05）。CPR组和EPO组ROSC120minLVEDP（mmHg／s）均较正常对照组明显升高（22．94±3．94、11．18±2．58比2．89±0．70，均P〈0．01），EPO组LVEDP则较CPR组明显下降徊〈0．05）。光镜和电镜下观察，CPR组心肌细胞坏死、炎性细胞浸润，心肌细胞胞膜完整性丧失、线粒体肿胀，心肌细胞凋亡增加[凋亡细胞数（个）：314．1±30．7比165．2±45．9，P〈0．013；经EPO干预后心肌病理损伤减轻，心肌细胞凋亡较CPR组减少（凋亡细胞数：242．1±20．0比314．1±30．7，P〈0．05）。CPR组和EPO组ROSC120min血清cTnl（μg／L）均较正常对照组明显升高（20．70±5．96、16．98±3．81比2．60±0．86，均P〈0．01），而CPR组和EPO组比较无差异。结论EPO可以改善窒息性心搏骤停大鼠CPR后的心功能，减轻心肌损伤，其机制可能与减少线粒体损伤和心肌细胞凋亡有关。
Objective To examine the effects of EPO administration on the integrity of myocardium in a rat model of asphyxia-induced cardiac arrest/CPR. Methods 24 male Sprague-Dawley （SD） rats were randomly divided into three groups （8 each） to receive （1） cardiac arrest （induced by tracheal catheter clamping for 8 minutes）/CPR （by chest compressions and mechanical ventilation 8 minutes after cardiac arrest）, （2） cardiac arrest/CPR5＋EPO （5 kU/kg, i. v, 3 minutes after restoration of spontaneous circulation （ROSC）, and （3） no-treatment （control）. The left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP）, and maximal positive/negative filling pressure change versus time （5=dp/dt max） in the animals were recorded 30, 60, 90, and 120 minutes after ROSC. Blood and heart tissue samples were collected 120 minutes after ROSC for the examination of serum troponin I （cTnI） level, myocardium pathological change （by light/electronic microscopy）, and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick endlabeling （TUNEL） staining]. Results The LVSP, ＋dp/dt max and -dp/dt max absolute value in CPR group and EPO group were significantly lower than that of baseline at 30, 60, 90, 120 minutes after ROCS. In comparision with the control group, the LVSP （mm Hg, 1 mm Hg = 0. 133 kPa ： 119.52 ± 12.68, 134.32 5= 15.78 vs. 165.82 ± 7.05）, ＋ dp/dt max （ram Hg/sec： 4 457.14 5= 826.22, 6 019.85 5= 1 192.19 vs. 10 325.93 ± 773.09）, and -dp/dt max （mm Hg/sec： 3 956.045=952.37, -4 957.225=838.60 vs. -8 421.335=886.65） were significant lower （all P〈0.01） in the CPR and EPO group 30 minutes after ROSC, and such tendency remained till 120 minutes after ROSC： （LVSP： 124.62 ± 8.07, 145.61 5= 16.70 vs. 162.34 ±7.63; 5= dp/dt max.. 4 977.67±350.40, 7 471.62 5= 998.32 vs. 9 999.39 5= 727.96; - dp/dt max： 4 145.51 51± 729.77,-5 895.64±787.30 vs. -8 089.75 ± 981.52）. Compared to the CPR group, the value of LVSP,＋ dp/dt max and - dp/dt max at all time points were significantly higher in EPO group （all P〈0. 05）. The LVEDP value was significantly higher （P〈0.01） in both CPR and EPO group in comparison with the control （mm Hg/sec： 22.94±3.94, 11.18± 2.58 vs. 2.89± 0.70） 120 minutes after ROSC, and it was significantly lower in EPO group in comparision with CPR group （P 〈 0. 05）. Light/electronic microscopy revealed myocardial necrosis, inflammatory cell infiltration, myocardial cell membrane integrity loss, mitochondrial swelling, and increased number of apoptotic cardiomycocyte （314. 1±30.7 vs. 165.2±45.9 as in control） in CPR group samples. In contrast, the cardiomycocyte morphologic damages were significantly fewer in EPO group, so is the numbers of apoptotic cardiomycocyte （242.1 ±20.0 vs. 314.1 ± 30. 7, P〈0. 05）. In comparison with the control, the serum cTnI 120 minutes after ROSC was significantly higher （all P〈0. 01） in CPR and EPO group （μg/L： 20. 70±5.96,16.98±3.81 vs. 2.60± 0. 86）, but no such difference was found between these two groups. Conclusion EPO can attenuate the post resuscitation myocardial injury probably through its mitochondrial protective, anti-apoptotic effect.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2011年第10期608-612,共5页
Chinese Critical Care Medicine
基金
广东省医学科研基金立项课题
关键词
促红细胞生成素
心搏骤停
缺血/再灌注损伤
心肌
心功能不全
心肺复苏
Erythropoietin
Cardiac arrest
Myocardium ischemia/reperfusion injury
Myocar- dium
Myocardial dysfunction
Cardiopulmonary resuscitation
