萝卜硫素对猪心肺复苏后急性肺损伤的保护作用及机制  

The protective effects of sulforaphane on acute lung injury after cardiopulmonary resuscitation in pigs and its mechanism

作　　者：张龚平 谢璐涛 卢晓驰 杨雪林[1] 潘群婕[1] 兰频[1] Zhang Gong-ping;Xie Lu-tao;Lu Xiao-chi;Yang Xue-lin;Pan Qun-jie;Lan Pin(Department of Emergency Medicine,Lishui Municipal Central Hospital,Lishui 323000,China)

机构地区：[1]丽水市中心医院急诊医学科,浙江丽水323000

出　　处：《中国急救医学》2023年第5期393-398,共6页Chinese Journal of Critical Care Medicine

基　　金：丽水市科技计划项目(2022SJZC015,2022GYX36,2023GYX24)。

摘　　要：目的 探讨萝卜硫素(SFN)对猪心肺复苏(CPR)后急性肺损伤(ALI)的保护作用及潜在机制。方法 选择24头普通级大白猪,应用随机数字表法分为假手术组(n=6)、模型组(n=9)和SFN组(n=9)。选择右心室放电诱导心脏骤停(CA)10 min与CPR 6 min的方法建立室颤型猪CA/CPR模型。于造模成功后5 min时,SFN组经股静脉泵入SFN 2 mg/kg,整个时长10 min。于造模前及造模后4 h观察期间,应用脉波指示连续心排血量监测(PiCCO)模块定期检测血管外肺水指数(ELWI)和肺血管通透性指数(PVPI)的变化。于造模后24 h处死动物并获取左肺下叶组织样本,应用凋亡细胞检测(TUNEL)法检测肺组织细胞凋亡指数,以及免疫印迹试验(Western Blot)法检测活化型半胱氨酸天冬氨酸蛋白酶3(cleaved caspase 3)、受体相互作用蛋白3 (RIP3)和混合谱系激酶域样蛋白(MLKL)的表达水平。结果 (1)造模前,各组猪的ELWI和PVPI值处于一致的生理水平,组间比较差异无统计学意义(均P>0.05)。造模后,与假手术组比较,模型组各时间点ELWI和PVPI值均显著上升,SFN组2 h内ELWI值和各时间点PVPI值均显著上升(均P<0.05)。但与模型组比较,SFN组造模2 h后ELWI值和1 h后PVPI值均显著下降(均P<0.05)。(2)造模后24 h,与假手术组比较,模型组和SFN组肺组织细胞凋亡指数显著升高,cleaved caspase 3、RIP3和MLKL的蛋白表达水平显著增加(均P<0.05)。但与模型组比较,SFN组肺组织细胞凋亡指数显著降低,cleaved caspase-3、RIP3和MLKL的蛋白表达水平显著减少(均P<0.05)。结论 SFN能有效减轻猪CPR后ALI程度,同时产生积极的保护作用,其保护途径与抑制肺组织细胞凋亡和坏死性凋亡有关。Objective To explore the protective effects of sulforaphane(SFN) on acute lung injury(ALI) after cardiopulmonary resuscitation in pigs and its potential mechanism.Methods Twenty-four conventional white pigs were chosen and were randomly divided into the following groups by using a random number table:sham group(n=6),model group(n=9),and SFN group(n=9).The study chose to establish the porcine model of ventricular fibrillation-related cardiac arrest(CA) and cardiopulmonary resuscitation(CPR) based on the methods including 10 min of CA electrically induced by the right ventricle and then 6 min of CPR.At 5 min after the animal model establishment,a dose of 2 mg/kg SFN was infused via the femoral vein within 10 min in the SFN group.Prior to the model establishment and during 4 h observation after the model establishment,the changes of extravascular lung water index(ELWI) and pulmonary vascular permeability index(PVPI) were regularly measured by using PiCCO monitor.At 24 h after the model establishment,the animals were sacrificed and their left lower lung lobe's tissue specimens were obtained to detect the index of cell apoptosis by TUNEL assay,and the protein expression levels of cleaved caspase 3,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL) by Western blot.Results(1)Prior to the model establishment,the values of ELWI and PVPI were kept at an even physiological level in the three groups(all P>0.05).After the model establishment,the values of ELWI and PVPI at different time points in the model group were significantly increased,and the values of ELWI within 2 h and the values of PVPI at different time points in the SFN group were significantly elevated when compared with the sham group(all P<0.05).However,the values of ELWI at 2 h after the model establishment and the values of PVPI at 1 h after the model establishment were significantly decreased in the SFN group when compared to the model group(all P<0.05).(2) At 24 h after the model establishment,the index of cell apoptosis

关 键 词：萝卜硫素(SFN) 心脏骤停(CA) 心肺复苏(CPR) 急性肺损伤(ALI) 肺组织 细胞凋亡 坏死性凋亡 猪 

分 类 号：R541.78[医药卫生—心血管疾病]