胞二磷胆碱提高心肺复苏效果和减轻心肌损伤的作用研究

The effects of CDP-Choline on the improvement of the successful rate of cardiopulmonary resuscitation and post-resuscitation cardiac function

目的探讨胞二磷胆碱在心肺复苏（CPR）中对于提高自主循环恢复（ROSC）率和减轻心脏损伤的作用。方法按随机数字表法将SD大鼠分为对照组（未窒息，5只）、模型组（10只）、肾上腺素组（10只）、胞二磷胆碱组（10只），用窒息法复制心搏骤停（CA）动物模型并进行CPR，各组分别于复苏前5min和复苏开始时给2次药，对照组和模型组给予等量生理盐水。各组于CPR期间及复苏成功后2h内测定血流动力学指标，然后处死大鼠取心脏组织，检测ATP酶、超氧化物歧化酶（SOD）、丙二醛（MDA）水平，评估大鼠心肌缺血／再灌注损伤情况。结果胞二磷胆碱组和肾上腺素组ROSC率高于模型组（90％、80％比20％，均P〈0．01），平均复苏时间（S）显著短于模型组（53±10、55±9比95±7，均P〈0．01）；复苏后2h末心率（HR，次／min）、平均动脉压（MAP，mmHg，1mmHg=0．133kPa）均显著高于模型组（HR：222．78±41．55、167．75±11．76比131．50±0．70，MAP：36．53±8．69、39．30±6．45比30．19±5．15，均P〈0．01）。胞二磷胆碱组复苏后心功能[左室内压上升／下降最大速率（±dp／dtmax）]逐渐平稳并显著高于模型组和肾上腺素组；肾上腺素组虽高于模型组，但下降趋势明显。胞二磷胆碱组Na＋-K＋-ATP酶（μmol·mg-1·h-1）和SOD活性（U／mg）显著高于模型组和肾上腺素组（Na＋-K＋-ATP酶：7．35±0．20比5．11±0．69、4．70±0．41，SOD活性：320．65±47．25比225．79±24．64、253．67±12．00，均P〈0．01），而MDA含量（mmol／mg）显著低于模型组和肾上腺素组（8．19±1．64比16．59±1．27、14．65±0．93，均P〈0．01），且上述指标与对照组比较无明显差异；模型组和肾上腺素组上述各指标也无明显差异。结论胞二磷胆碱可提高CPR成功率，并且与肾上腺素相比可减轻心肌缺血／再灌注损伤，改善复苏后心功能。

Objective To investigate the effects of CDP-Choline on the improvement of recovery of spontaneous circulation （ROSC） and protection against myocardial injury in eardiopulmonary resuscitation （CPR）. Methods Sprague-Dawley （SD） rats were randomized into four groups： control group （n = 5, no asphyxia）, model group （ n = 10）, adrenaline group （ n = 10 ） and CDP-Choline group （ n = 10 ）. Cardiac arrest （ CA ） was induced by asphyxia, and then CPR was initiated. Drugs were administered at 5 minutes before CPR and at the initiation of CPR. Equal amount of normal saline was given in the control group and the model group. The hemodynamic parameters were monitored during CPR and after ROSC. After 2 hours, the myocardial tissue of the rats was harvested to assess the degree of ischemia/reperfusion （I/R） injury by measuring ATPase activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） content. Results Compared with the model group, the rate of ROSC was significantly elevated （90%, 80% vs. 20%, both P〈0.01） in the CDP-Choline group and the adrenaline group, the time of achieving ROSC （s） was shorter （53 ± 10, 55 ± 9 vs. 95 ± 7, both P〈0.01 ）, and the heart rate （HR, bpm） and mean arterial pressure （MAP, mm Hg, 1 mm Hg=0.133 kPa） at 2 hours after CPR were higher （HR： 222.78 ±41.55, 167.75 ± 11.76 vs. 131.50 ± 0.70; MAP： 36.53 ± 8.69, 39.30±6.45 vs. 30.19±5.15, all P〈0.01）. The cardiac function [the maximal rate of left ventricular pressure increase/decline （ ± dp/dt max）] in the CDP-Choline group was gradually stabilized and significantly higher than that in the model and the adrenaline groups. The cardiac function in the adrenaline group was higher than that of the model group, but it was in a tendency of lowering. Compared with the model group and the adrenaline group, the reduction of Na＋-K＋-ATPase （μmol·mg-1·h-1） and SOD （U/mg） activity were significantly increased in the CDP-Choline group （Na＋-K＋-ATPase： 7.35±0.20 vs. 5.11 ±0.69, 4.70 ± 0.41; SOD activity： 320.65 ± 47.25 vs. 225.79 ± 24.64,253.67 ± 12.00, all P〈0.01 ）, and myocardial MDA （mmol/mg） content in the CDP-Choline group was significantly lower than that in the model group and the adrenaline group （8.19 ± 1.64 vs. 16.59 ± 1.27, 14.65±0.93, both P〈0.01 ） . There was no significant difference in the measured parameters between the CDP-Choline group and the control group, and also between the model group and the adrenaline group. Conclusion CDP-Choline has the effect on improvement of the successful rate of CPR, and it shows an obvious myocardial protection against I/R compared with adrenaline.