氢溴酸山莨菪碱对心肺复苏术后冠脉内皮功能的保护作用机制  

Protective mechanism of anisodamine hydrobromide on coronary endothelial function after cardiopulmonary resuscitation

作　　者：王福军[1] 杨军[1] 张健[1] 王宏伟[1] 赵鑫 董桂娟 冯安琪 翟文亮 郭树彬[1] Wang Fu-jun;Yang Jun;Zhang Jian;Wang Hong-wei;Zhao Xin;Dong Gui-juan;Fen An-qi;Zhai Wen-liang;Guo Shu-bin(Emergency Department,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院急诊科,北京100020

出　　处：《中国急救医学》2021年第1期60-65,共6页Chinese Journal of Critical Care Medicine

摘　　要：目的探讨氢溴酸山莨菪碱(654-1)对室颤导致心脏骤停心肺复苏术后猪冠脉内皮损伤的影响。方法建立室颤实验动物猪模型,分为三个组:假手术组(S组,n=6)、室颤组(VF组,n=8)和654-1干预组(VF-6组,n=8)。在心肺复苏自主循环恢复(ROSC)后0.5 h经股静脉给予654-1(4 mg/kg),分别记录每组实验动物基础状态,ROSC即刻、1、2、4和6 h的舌下灌注血管密度(perfusion vessel density,PVD)。ROSC后6 h处死动物,取冠脉前降支组织标本进行HE染色、酶联免疫吸附方法(ELISA)、Western Blot等方法检测,对冠脉血管内皮完整性、上皮细胞形态及冠脉组织syndecan-1、TNF-α水平、半胱氨酸蛋白酶3(Caspase 3)进行比较分析。结果与S组比较,VF组冠脉HE染色显示冠脉内皮细胞受到破坏,细胞排列不连续、细胞脱落、细胞核浓缩并变形;与S组比较,VF组PVD下降(11.520±3.073 vs.7.642±2.766,P=0.001),冠脉组织syndecan-1(0.387±0.095 vs.1.221±0.238,P=0.009)、TNF-α(0.295±0.290 vs.3.972±1.203,P=0.002)、Caspase 3(139.4±51.2 vs.399.4±128.5,P=0.004)水平明显升高。与VF组比较,VF-6组舌下微循环PVD升高(7.642±2.766 vs.11.350±2.954,P=0.001),冠脉组织syndecan-1(1.221±0.238 vs.0.557±0.279,P=0.004)、TNF-α(3.972±1.203 vs.1.155±0.681,P=0.009)、Caspase 3(399.4±128.5 vs.241.0±61.7,P=0.026)表达水平明显降低。结论心脏骤停心肺复苏术后,654-1通过改善微循环达到抑制炎症因子释放,保护冠脉内皮糖萼,减少冠脉上皮细胞凋亡,从而保护冠脉内皮功能。Objective To investigate the effect of anisodamine hydrobromide(654-1) on the injury of coronary artery endothelium after cardiopulmonary resuscitation(CPR) in the pig models of ventricular fibrillation. Methods The pig models of ventricular fibrillation were established and divided into three groups: sham group(S group,n = 6),ventricular fibrillation group(VF group,n = 8),and654-1 intervention group(VF-6,n = 8). 654-1(4 mg/kg) were injected by femoral vein half an hour after cardiopulmonary resuscitation(ROSC),and basic condition and sublingual perfusion vessel density(PVD) immediately,1 h,2 h,4 h and 6 h after ROSC in each group were recorded. Six hours after ROSC,the animals were killed. The samples of anterior descending coronary artery were detected by HE staining,enzyme-linked immunosorbent assay(ELISA) and Western blot. The vascular endothelial integrity,epithelial cell morphology,levels of syndecan-1 and TNF-and Caspase 3 were compared and analyzed. Results Compared with S group,coronary artery HE staining showed that the coronary endothelial cells were destroyed,the cell arrangement was discontinuous,the cells fell off,the nucleus condensed and deformed in VF group;Compared with S group,PVD decreased(11. 520 ±3. 073 vs. 7. 642 ± 2. 766,P = 0. 001),and serum syndecan-1(0. 387 ± 0. 095 vs. 1. 221 ± 0. 238,P = 0. 009),the levels of TNF-(0. 295 ± 0. 290 vs. 3. 972 ± 1. 203,P = 0. 002) and Caspase 3 increased in VF group(139. 4 ± 51. 2 vs. 399. 4 ± 128. 5,P = 0. 004). Compared with VF group,sublingual microcirculation PVD in VF-6 group increased(7. 642 ± 2. 766 vs. 11. 350 ± 2. 954,P =0. 001),and syndecan-1(1. 221 ± 0. 238 vs. 0. 557 ± 0. 279,P = 0. 004),TNF-(3. 972 ± 1. 203 vs.1. 155 ± 0. 681,P = 0. 009),Caspase 3(399. 4 ± 128. 5 vs. 241. 0 ± 61. 7,P = 0. 026) decreased significantly,which suggested that 654-1 had protective effect on coronary endothelium. Conclusion After CPR,654-1 can inhibit the release of inflammatory factors,protect the glycocalyx of coronary artery endothelium and reduc

关 键 词：氢溴酸山莨菪碱(654-1) 心肺复苏 冠脉内皮 微循环 

分 类 号：R965[医药卫生—药理学]