参麦注射液对家兔心脏骤停后综合征影响的实验研究

Experimental study of the effect of Shenmai injection on post-cardiac arrest syndrome in rabbit

目的 观察参麦注射液对家兔心脏骤停后综合征（PCAS）的治疗效果,探讨其作用机制.方法 将73只健康成年新西兰大白兔按随机数字表法分为假手术组（n=10）、模型组（n=21）和高、低剂量参麦组（n=21）.采用气管夹闭窒息法建立家兔心搏骤停模型；假手术组不进行气管夹闭窒息,仅给予麻醉和气管切开.分别于窒息前及自主循环恢复（ROSC）后3、6、12、24、48 h检测各组动物血清肌酸激酶同工酶（CK-MB）、丙氨酸转氨酶（ALT）、肌酐（Cr）、肌钙蛋白Ⅰ（cTnI）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-1β、IL-6）及核转录因子-κB（NF-κB）的水平,比较各组家兔各项指标的动态变化.结果 高、低剂量参麦组及模型组家兔ROSC后各指标均逐渐升高,IL-6于6h达峰值,IL-1β于12h达峰值,CK-MB、cTnI、TNF-α、NF-κB于24h达峰值,而ALT、Cr于48 h达峰值.高剂量参麦组于ROSC后6h起血CK-MB、ALT、cTnI水平即明显低于模型组[CK-MB（U/L）：571.69±24.39比587.98±22.38,ALT（U/L）：74.88±8.71比81.49±5.79,cTnI（μg/L）：7.82±1.52比8.97±1.87],12h起血TNF-α、NF-κB明显低于模型组[TNF-α （ng/L）：120.36±12.38比135.23±20.13,NF-κB（ng/L）：2.18±0.17比2.29±0.15],24 h起血IL-1β、IL-6明显低于模型组[IL-1β（ng/L）：1.49±0.13比1.62±0.17,IL-6（ng/L）：72.01±5.02比79.35±11.28],而Cr仅于24 h时较模型组明显降低（μmol/L：158.73±4.40比162.97±5.02,P＜0.05或P＜0.01）.低剂量参麦组ROSC后24 h起血CK-MB、Cr、cTnI水平才明显低于模型组[CK-MB（U/L）：1 769.00±19.73比2 120.96±24.15,Cr（μmol/L）：159.32±3.02比162.97±5.02,cTnI（μg/L）：12.17±3.04比14.89±3.09,P＜0.05或P＜0.01],而ROSC后各时间点ALT、TNF-α、IL-1β、IL-6、NF-κB水平与模型组比较差异均无统计学意义.高剂量参麦组ROSC后6h、12h血CK-MB、cTnI及24h血TNF-α、IL-6明显低于低剂量参麦组（均P＜0.05）.结论 心搏骤停复苏后家兔各器官损伤严重程度与血中细胞因子TNF-α、IL-1β、IL-6、NF-κB水平动态变化相关；心肺复苏后早期应用参麦注射液可抑制或减轻PCAS的发生发展,尤其对复苏后缺血、缺氧的心肌细胞具有一定的保护作用.

Objective To observe the effects of Shenmai injection on post-cardiac arrest syndrome （PCAS） in rabbit and to discuss the underlying mechanism.Methods Seventy-three rabbits were divided into sham operation group （n＝-10）,model group （n=21）,high and low dosage Shenmai group （each n=21） by random number table method.The animal model of cardiac arrest was reproduced by clamping the endotracheal tube.The rabbits in sham operation group were only given anesthesia and tracheostomy without producing asphyxia by clamping the trachea to produce asphyxia.Serum creatine kinase isoenzyme （CK-MB）,alanine aminotransferase （ALT）,creatinine （Cr）,troponin Ⅰ （cTnI）,tumor necrosis factor-α （TNF-α）,interleukin （IL-1 β,IL-6） and nuclear transcription factors-κB （NF-κB） levels were determined before asphyxia and 3,6,12,24,48 hours after restoration of spontaneous circulation （ROSC）,and dynamic changes in various parameters were determined in each group.Results All the indexes in model group and Shenmai groups were gradually increased after ROSC.IL-6 peaked at 6 hours,IL-1βpeaked at 12 hours,CK-MB,cTnI,TNF-α and NF-κB peaked at 24 hours, ALT and Cr peaked at 48 hours.CK-MB,ALT,cTnI levels in high dosage Shenmai group were significandy lower than those in the model group 6 hours after ROSC [CK-MB （U/L）：571.69 ± 24.39 vs.587.98 ± 22.38,ALT （U/L）：74.88 ± 8.71 vs.81.49 ± 5.79,cTnI （μg/L）：7.82 ± 1.52 vs.8.97 ± 1.87],serum levels of TNF-α and NF-κB 12 hours after ROSC [TNF-α （ng/L）：120.36 ± 12.38 vs.135.23 ± 20.13,NF-κB （ng/L）：2.18 ± 0.17 vs.2.29 ± 0.15],and the serum levels of IL-1β and IL-6 24 hours after ROSC in high dose Shenmai group were significantly lower than those in the model group [IL-1β（ng/L）：1.49 ± 0.13 vs.1.62 ± 0.17,IL-6 （ng/L）：72.01 ± 5.02 vs.79.35 ± 11.28],however,serum Cr in high dosage Shenmai group was significantly lower than in the model group at 24 hours after ROSC （μmol/L：158.73 ± 4.40 vs.162.97 ±5.02,P＜0.05 or P＜0.01）.In low dosage Shenmai group,the serum level of CK-MB,Cr,cTnI were significantly lower than those in the model group 24 hours after ROSC [CK-MB （U/L）：1 769.00 ± 19.73 vs.2 120.96 ± 24.15,Cr （μmol/L）：159.32 ± 3.02 vs.162.97 ± 5.02,cTnI （μg/L）：12.17 ± 3.04 vs.14.89 ± 3.09,P＜0.05 or P＜0.01）.But after ROSC,ALT,TNF-α,IL-1β,IL-6 and NF-κB showed no significant change as compared with model group.In high dosage Shenmai group,serum levels of CK-MB and cTnI at 6,12 hours and TNF-α and IL-6 at 24 hours after ROSC were significantly lower than those in the low dosage Shenmai group （all P＜0.05）.Conclusions Severity of injury of different organs in rabbit cardiac arrest model showed positive correlation with the alterations in serum TNF-α,IL-1β,IL-6,NF-κB after cardiopulmonary resuscitation.Early use of Shenmai injection after cardiopulmonary resuscitation can retard the development of PCAS,especially in the protection of ischemia and hypoxia of myocardium after cardiopulmonary resuscitation.