摘要目的 探讨促红细胞生成素(EPO)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8 min建立窒息性心搏骤停-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8 min予胸外按压和机械通气进行复苏；EPO组于自主循环恢复(ROSC)后3 min股静脉注射EPO 5 kU/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/dt max)等血流动力学指标.于观察终点(ROSC后120 min)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、120 min时LVSP、+dp/dt max和- dp/dt max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ROSC 30 min时LVSP(mm Hg,1 mm Hg=0.133 kPa)、+dp/dt max(mm Hg/s)、- dp/dt max绝对值(mm Hg/s)即明显下降(LVSP:119.52±12.68、134.32±15.78比165.82土7.05; +dp/dt max:4 457.14±826.22、6 019.85±1 192.19比10 325.93±773.09; - dp/dt max:-3 956.04±952.37、-4 957.22±838.60比-8 421.33±886.65,均P＜0.01),并持续至ROSC 120 min(LVSP:124.62±8.07、145.61±16.70比162.34±7.63; +dp/dt max:4 977.67±350.40、7 471.62±998.32比9 999.39±727.96;- dp/dt max:-4 145.51±729.77、-5 895.64±787.30比-8 089.75±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ROSC 120 min LVEDP(mm Hg/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(P＜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＜0.01]；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ROSC 120 min血清cTnI (μg/L)均较正常对照组明显升高(20.70土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.

abstractsObjective 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/CPR+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 (士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 (cTnl) level,myocardium pathological change (by light/electronic microscopy),and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated Dutp-biotin nick endlabeling (TUNEL) stainingl.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,I mm Hg= 0.133 kPa:119.52土 12.68,134.32土 15.78 vs. 165.82士 7.05),+dp/dt max (mm Hg/sec:4 457.14士 826.22,6 019.85士 I 192.19 vs.10 325.93土 773.09),and -dp/dt max (mm Hg/sec:- 3 956.04土 952.37,- 4 957.22± 838.60 vs.- 8 421.33土 886.65) were significant lower (alIP<O.OI) in the CPR and EPO group 30 minutes after ROSC,and such tendency remained till 120 minutes after ROSC:(LVSP:124.62士 8.07,145.61士 16.70 vs. 162.34士 7.63; + dp/dt max:4 977.67土350.40,7 471.62士 998.32 vs. 9 999.39土 727.96; - dp/dt max:- 4 145.51土 729.77,-5 895.64士787.30 vs.- 8 089.75士 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<O.05).The LVEDP value was significantly higher (P<O.01) in both CPR and EPO group in comparison with the control (mm Hg/sec:22.94士3.94,11.18士 2.58 vs.2.89士0.70) 120 minutes after ROSC,and it was significantly lower in EPO group in comparision with CPR group (P<O.05).Light/electronic nucroscopy 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土45.9 as in control) in CPR group samples.In contrast,the cardiomycocyte morphologic damages were signi~icantly fewer in EPO group,so is the numbers of apoptotic cardiomycocyte (242.1士 20.O vs.314.1土 30.7,P< 0.05).In comparison with the control,the serum cTnl 120 minutes after ROSC was significantly higher (all P<O.01) in CPR and EPO group (Vg/L:20.70士5.96,16.98士3.81 vs.2.60士 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.