Chunling Ji, Hourong Zhou, Xiulin Yang, Qian Zhang, Yuhui Yuan, Jia Huang
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015 Dec;27(12):984-8. doi: 10.3760/cma.j.issn.2095-4352.2015.12.009.
To study the protective effect of erythropoietin (EPO) on brain tissue with cardiac arrest-cardiopulmonary resuscitation (CA-CPR) and its mechanism.
120 male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 40), namely: sham group, routine chest compression group, and conventional chest compression + EPO group (EPO group). The rats in each group were subdivided into CA and 6, 12, 24, 48 hours after restoration of spontaneous circulation (ROSC) five subgroups (each n = 8). The model of CA was reproduced according to the Hendrickx classical asphyxia method followed by routine chest compression, and the rats in sham group only underwent anesthesia, tracheostomy intubation and venous-puncture without asphyxia and CPR. The rats in EPO group were given the routine chest compression + EPO 5 kU/kg (2 mL/kg) after CA. Blood sample was collected at different time points of intervention for the determination the content of serum S100 β protein by enzyme linked immunosorbent assay (ELISA). All the rats were sacrificed at the corresponding time points, and the hippocampus was harvested for the calculation of the number of S100 β protein positive cells, and to examine the pathological changes and their scores at 24 hours after ROSC by light microscopy.
With prolongation of ROSC time, the serum levels of S100 β protein (µg/L) in the routine chose compression group and the EPO group were significantly elevated, peaking at 24 hours (compared with CA: 305.7 ± 29.2 vs. 44.4 ± 6.2 in routine chest compression group, and 276.7 ± 28.9 vs. 44.7 ± 5.6 in the EPO group, both P < 0.05), followed by a fall. The levels of S100 β protein at each time point after ROSC in EPO group were significanthy lower than those of the routine chest compression group (83.2 ± 7.5 vs. 114.3 ± 15.3 at 6 hours, 123.9 ± 20.2 vs. 184.9 ± 22.2 at 12 hours, 276.7 ± 28.9 vs. 305.7 ± 29.2 at 24 hours, 256.3 ± 26.6 vs. 283.2 ± 23.6 at 48 hours, all P < 0.05). With the prolongation of ROSC time, the S100 β protein positive cell number in brain (cells/HP) in the routine chest compression group and the EPO group was significantly increased, peaking at 24 hours (compared with CA: 14.3 ± 2.2 vs. 6.7 ± 0.7 in the routine chest compression group, 11.3 ± 1.3 vs. 6.8 ± 0.9 in the EPO group, both P < 0.05), then it began to fall. The S100 β protein positive cell number in brain at each time point after ROSC in the EPO group was significantly lower than that of the routine chest compression group (7.0 ± 0.9 vs. 7.9 ± 1.9 at 6 hours, 8.4 ± 1.1 vs. 10.2 ± 2.2 at 12 hours, 11.3 ± 1.3 vs. 14.3 ± 2.2 at 24 hours, 8.3 ± 0.8 vs. 10.8 ± 2.0 at 48 hours, all P < 0.05). Under the light microscope, a serious brain cortex injury was found after reproduction of the model, and the degree of injury was reduced after EPO intervention. The pathological score at 24 hours after ROSC in EPO group was lower than that of routine chest compression group (3.83 ± 0.73 vs. 4.17 ± 0.75, P < 0.05).
The S100 β protein level in serum and brain tissue was increased early in asphyxia CA-CPR rats. EPO intervention can reduce the expression of S100 protein and reduce the degree of brain injury.
研究促红细胞生成素（EPO）对心脏骤停-心肺复苏（CA-CPR）后脑组织的保护作用及其机制。
将120只雄性Sprague-Dawley（SD）大鼠随机分为三组（每组n = 40），即：假手术组、常规胸外按压组和常规胸外按压+EPO组（EPO组）。每组大鼠再分为心脏骤停及自主循环恢复（ROSC）后6、12、24、48小时五个亚组（每组n = 8）。按照Hendrickx经典窒息法复制心脏骤停模型后进行常规胸外按压，假手术组大鼠仅行麻醉、气管切开插管及静脉穿刺，不行窒息及心肺复苏。EPO组大鼠在心脏骤停后给予常规胸外按压+EPO 5 kU/kg（2 mL/kg）。在干预的不同时间点采集血样，采用酶联免疫吸附测定（ELISA）法测定血清S100β蛋白含量。所有大鼠在相应时间点处死，取海马计算S100β蛋白阳性细胞数，并在ROSC后24小时通过光学显微镜观察病理变化及其评分。
随着ROSC时间延长，常规胸外按压组和EPO组血清S100β蛋白水平（μg/L）显著升高，在24小时达到峰值（与心脏骤停时相比：常规胸外按压组为305.7±29.2 vs. 44.4±6.2，EPO组为276.7±28.9 vs. 44.7±5.6，均P < 0.05），随后下降。ROSC后各时间点EPO组S100β蛋白水平均显著低于常规胸外按压组（6小时：83.2±7.5 vs. 114.3±15.3，12小时：123.9±20.2 vs. 184.9±22.2，24小时：276.7±28.9 vs. 305.7±29.2，48小时：256.3±26.6 vs. 283.2±23.6，均P < 0.05）。随着ROSC时间延长，常规胸外按压组和EPO组脑内S100β蛋白阳性细胞数（细胞/HP）显著增加，在24小时达到峰值（与心脏骤停时相比：常规胸外按压组为14.3±2.2 vs. 6.7±0.7，EPO组为11.3±1.3 vs. 6.8±0.9，均P < 0.05），然后开始下降。ROSC后各时间点EPO组脑内S100β蛋白阳性细胞数均显著低于常规胸外按压组（6小时：7.0±0.9 vs. 7.9±1.9，12小时：8.4±1.1 vs. 10.2±2.2，24小时：11.3±1.3 vs. 14.3±2.2，48小时：8.3±0.8 vs. 10.8±2.0，均P < 0.05）。光学显微镜下，模型复制后可见严重的脑皮质损伤，EPO干预后损伤程度减轻。ROSC后24小时EPO组病理评分低于常规胸外按压组（3.83±0.73 vs. 4.17±0.75，P < 0.05）。
窒息性心脏骤停-心肺复苏大鼠血清和脑组织中S100β蛋白水平早期升高。EPO干预可降低S100蛋白表达，减轻脑损伤程度。
