青蒿素减轻心脏骤停-心肺复苏所致肺损伤的作用及机制  

Effect and mechanism of artemisinin on lung injury caused by cardiac arrest and cardiopulmonary resuscitation

作　　者：张龚平 谢璐涛 卢晓驰 杨雪林[1] 潘群婕[1] 兰频[1] ZHANG Gongping;XIE Lutao;LU Xiaochi(Department of Emergency Medicine,Lishui Central Hospital,Lishui 323000,CHINA)

机构地区：[1]丽水市中心医院急诊医学科,浙江323000

出　　处：《江苏医药》2024年第3期222-227,共6页Jiangsu Medical Journal

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

摘　　要：目的探讨青蒿素减轻心脏骤停-心肺复苏(CPR)所致肺损伤的作用及机制。方法22头大白猪随机分为假手术(S)组(6头)、CPR组(8头)和CPR+青蒿素组(8头)。CPR组和CPR+青蒿素组采用电刺激诱导心脏骤停9 min与人工CPR 6 min的方法建立猪CPR模型。造模成功后,CPR+青蒿素组在2 h内静脉匀速泵入青蒿素4.8 mg/kg,S组和CPR组采用相同方法给予等量生理盐水。于造模前及造模后1、2、4 h,应用脉搏指示连续心排血量监测仪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,采用Western blot法检测NOD样受体热蛋白结构域相关蛋白3(NLRP3)、剪切型Caspase-1(cleaved Caspase-1)和消皮素D-N端(GSDMD-N)蛋白表达,ELISA法检测IL-1β和IL-18含量。结果与S组相比,在造模后1、2、4 h时CPR组ELWI和PVPI升高,在造模后1、2 h时CPR+青蒿素组PVPI升高(P<0.05)。与CPR组相比,在造模后2、4 h时CPR+青蒿素组ELWI和PVPI降低(P<0.05)。与S组相比,CPR组和CPR+青蒿素组肺组织中cleaved Caspase-1和GSDMD-N蛋白表达及IL-1β和IL-18含量升高(P<0.05)。与CPR组相比,CPR+青蒿素组肺组织中NLRP3、cleaved Caspase-1和GSDMD-N蛋白表达及IL-1β、IL-18含量下降(P<0.05)。结论青蒿素能抑制猪心脏骤停-CPR后肺组织中NLRP3炎症小体介导的细胞焦亡过程,从而减轻心脏骤停-CPR所致肺损伤。Objective To explore the effect and mechanism of artemisinin on the lung injury caused by cardiac arrest and cardiopulmonary resuscitation(CPR).Methods Twenty-two white pigs were randomly divided into three groups of S(sham operation,6 pigs),C(underwent CPR,8 pigs)and T(underwent CPR+artemisinin,8 pigs).The CPR models were established in groups of C and T using electrical stimulation-induced cardiac arrest for 9 minutes and artificial CPR for 6 minutes.Artemisinin 4.8 mg/kg was infused intravenously within 2 hours after CPR modeling successfully in group T.Groups of S and C were infused the same amount of normal saline.The extravascular lung water index(ELWI)and pulmonary vascular permeability index(PVPI)were measured by pulse indicator continous cardiac output monitor at the time points of before(T0)and 1(T1),2(T2)and 4 hours(T3)after modeling.At 24 hours after modeling,the protein expressions of NOD-like receptor pyrin domain 3(NLRP3),cleaved Caspase-1 and gasdermin D-N terminal(GSDMD-N)were detected by Western blot,and IL-1β and IL-18 contents were detected by ELISA.Results Compared with group S,ELWI and PVPI in group C were increased at T1-T3,and PVPI in group T was increased at T1 and T2(P<0.05).Compared with group C,ELWI and PVPI in group T were decreased at T2 and T3(P<0.05).Compared with group S,the protein expressions of cleaved Caspase-1 and GSDMD-N,and the contents of IL-1β and IL-18 in groups of C and T were increased(P<0.05).Compared with group C,the protein expressions of NLRP3,cleaved Caspase-1 and GSDMD-N,and the contents of IL-1β and IL-18 in group T were decreased(P<0.05).Conclusion Artemisinin can reduce the lung injury caused by cardiac arrest and CPR by inhibiting NLRP3 inflammasome-mediated pyroptosis in pig lung tissues.

关 键 词：青蒿素 心脏骤停 心肺复苏 肺损伤 细胞焦亡 

分 类 号：R514[医药卫生—内科学]