Email Alert RSS
Volume 14 Issue 3
May  2023
Turn off MathJax
Article Contents
Abstract
References
Related Articles
LI Feng, WU Xinjie, CHEN Qijiang, LIU Ying, XU Jiefeng, ZHOU Guangju, ZHANG Mao. Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(3): 520-527. DOI: 10.12290/xhyxzz.2022-0730
Citation: LI Feng, WU Xinjie, CHEN Qijiang, LIU Ying, XU Jiefeng, ZHOU Guangju, ZHANG Mao. Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(3): 520-527. DOI: 10.12290/xhyxzz.2022-0730
shu

Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism

  • 1.

    Department of Emergency Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou 310009, China

  • 2.

    Department of Emergency Medicine, Linping Campus, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 311100, China

  • 3.

    Department of Emergency Medicine, The First Hospital of Ninghai, Ninghai, Zhejiang 315600, China

  • 4.

    Department of Intensive Care Unit, The First Hospital of Ninghai, Ninghai, Zhejiang 315600, China

  • 5.

    Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China

Funds: 

Natural Science Foundation of China 82072126

Zhejiang Provincial Key Research and Development Program 2021C03073

Zhejiang Provincial Key Research and Development Program 2021C03036

Zhejiang Provincial Medical Science Foundation 2023KY305

More Information
  • Corresponding author:

    ZHANG Mao, E-mail: z2jzk@zju.edu.cn

  • Received Date: December 28, 2022
  • Accepted Date: February 14, 2023
  • Issue Publish Date: May 29, 2023
    Graphical Abstract
    • Abstract
  •   Objective  To explore whether artesunate (Art) has protective effect on lung tissue after cardiopulmonary resuscitation (CPR) and its potential mechanism based on animal experiment.
      Methods  Twenty-four healthy male white pigs were randomly divided into sham group (n=6), CPR group (n=10), and Art group (n=8). The sham group only underwent the surgical preparation, and the CPR and Art groups established the CPR model by the method of ventricular fibrillation induction. After restoration of spontaneous circulation, the Art group was infused a dose of 4.8 mg/kg of Art via the femoral vein within 2 h. The same volume of vehicle was similarly infused in the sham and CPR groups. The changes of lung injury at baseline and after resuscitation, lung injury score, and lung tissue inflammation and its high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) inflammatory pathway after resuscitation were compared among the three groups.
      Results  (1) Lung injury: the levels of extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) at baseline were not significantly different among the three groups (all P > 0.05). The values of ELWI and PVPI at 1 h, 2 h, and 4 h after resuscitation were significantly increased while the values of OI at 1 h and 2 h after resuscitation were significantly decreased in the CPR group compared with the sham group (all P < 0.05). The values of ELWI, PVPI, and OI were better at each time point after resuscitation in the Art group than in the CPR group, in which the differences in ELWI and PVPI at 2 h and 4 h after resuscitation were significant between the two groups (all P < 0.05). (2)Lung injury score: the score of lung injury at 24 h after resuscitation was significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the score of lung injury at 24 h after resuscitation was significantly decreased in the Art group compared with the CPR group (P < 0.05). (3)Lung tissue inflammation: the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the lung at 24 h after resuscitation were significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the levels of TNF-α, IL-1β, and IL-6 in the lung at 24 h after resuscitation were significantly decreased in the Art group compared to the CPR group (all P < 0.05). (4) HMGB1/TLR4/NF-κB inflammatory pathway: the protein expression levels of HMGB1, TLR4, and NF-κB p65 in the lung at 24 h after resuscitation were significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the protein expression levels of HMGB1, TLR4, and NF-κB p65 in the lung at 24 h after resuscitation were significantly decreased in the Art group compared with the CPR group (all P < 0.05).
      Conclusions  Art could alleviate lung inflammatory injury after cardiac arrest and resuscitation, possibly through inhibiting the activation of HMGB1/TLR4/NF-κB signaling pathway.
    • FullText(HTML)
    • References (32)
  • [1]
    Xu F, Zhang Y, Chen Y. Cardiopulmonary resuscitation training in China: Current situation and future development[J]. JAMA Cardiol, 2017, 2: 469-470. DOI: 10.1001/jamacardio.2017.0035
    [2]
    Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: A report from the American Heart Association[J]. Circulation, 2022, 145: e153-e639.
    [3]
    Gräsner JT, Herlitz J, Tjelmeland IBM, et al. European Resuscitation Council guidelines 2021: Epidemiology of cardiac arrest in Europe[J]. Resuscitation, 2021, 161: 61-79. DOI: 10.1016/j.resuscitation.2021.02.007
    [4]
    Johnson NJ, Caldwell E, Carlbom DJ, et al. The acute respiratory distress syndrome after out-of-hospital cardiac arrest: Incidence, risk factors, and outcomes[J]. Resuscitation, 2019, 135: 37-44. DOI: 10.1016/j.resuscitation.2019.01.009
    [5]
    Ruwizhi N, Maseko RB, Aderibigbe BA. Recent advances in the therapeutic efficacy of artesunate[J]. Pharmaceutics, 2022, 14: 504. DOI: 10.3390/pharmaceutics14030504
    [6]
    Lohani N, Rajeswari MR. Dichotomous life of DNA binding high mobility group box1 protein in human health and disease[J]. Curr Protein Pept Sci, 2016, 17: 762-775. DOI: 10.2174/1389203717666160226145217
    [7]
    Xu J, Zhao X, Jiang X, et al. Tubastatin A improves post-resuscitation myocardial dysfunction by inhibiting NLRP3-mediated pyroptosis through enhancing transcription factor EB signaling[J]. J Am Heart Assoc, 2022, 11: e024205. DOI: 10.1161/JAHA.121.024205
    [8]
    Sordi R, Nandra KK, Chiazza F, et al. Artesunate protects against the organ injury and dysfunction induced by severe hemorrhage and resuscitation[J]. Ann Surg, 2017, 265: 408-417. DOI: 10.1097/SLA.0000000000001664
    [9]
    Khan AI, Kapoor A, Chen J, et al. The antimalarial drug artesunate attenuates cardiac injury in a rodent model of myocardial infarction[J]. Shock, 2018, 49: 675-681. DOI: 10.1097/SHK.0000000000000963
    [10]
    Chen Y, Wu J, Zhu J, et al. Artesunate provides neuroprotection against cerebral ischemia-reperfusion injury via the TLR-4/NF-κB pathway in rats[J]. Biol Pharm Bull, 2021, 44: 350-356. DOI: 10.1248/bpb.b20-00604
    [11]
    Ghoneim ME, Abdallah DM, Shebl AM, et al. The interrupted cross-talk of inflammatory and oxidative stress trajectories signifies the effect of artesunate against hepatic ischemia/reperfusion-induced inflammasomopathy[J]. Toxicol Appl Pharmacol, 2020, 409: 115309. DOI: 10.1016/j.taap.2020.115309
    [12]
    Liu Z, Zhang J, Li S, et al. Artesunate inhibits renal ischemia reperfusion-stimulated lung inflammation in rats by activating HO-1 pathway[J]. Inflammation, 2018, 41: 114-121. DOI: 10.1007/s10753-017-0669-3
    [13]
    Liu Z, Qu M, Yu L, et al. Artesunate inhibits renal ischemia-reperfusion-mediated remote lung inflammation through attenuating ROS-induced activation of NLRP3 inflammasome[J]. Inflammation, 2018, 41: 1546-1556. DOI: 10.1007/s10753-018-0801-z
    [14]
    Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria[J]. N Engl J Med, 2008, 358: 1829-1836. DOI: 10.1056/NEJMct0709050
    [15]
    Li Q, Cantilena LR, Leary KJ, et al. Pharmacokinetic profiles of artesunate after single intravenous doses at 0.5, 1, 2, 4, and 8 mg/kg in healthy volunteers: a phase I study[J]. Am J Trop Med Hyg, 2009, 81: 615-621. DOI: 10.4269/ajtmh.2009.09-0150
    [16]
    谢娜, 范开亮, 邵旭鹏, 等. 调气利水汤治疗中度急性呼吸窘迫综合征患者的临床研究[J]. 中国中医急症, 2022, 31: 789-792. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJZ202205009.htm
    [17]
    张汝敏, 王世富, 马爽, 等. PiCCO技术指导下不同呼气末正压水平对ARDS患者氧合的影响[J]. 中华急诊医学杂志, 2013, 22: 1398-1403.
    [18]
    Wu H, Xu S, Diao M, et al. Alda-1 treatment alleviates lung injury after cardiac arrest and resuscitation in swine[J]. Shock, 2022, 58: 464-469. DOI: 10.1097/SHK.0000000000002003
    [19]
    Wu C, Xu J, Jin X, et al. Effect of mild hypothermia on lung injury after cardiac arrest in swine based on lung ultrasound[J]. BMC Pulm Med, 2019, 19: 198. DOI: 10.1186/s12890-019-0958-8
    [20]
    徐杰丰, 吴春双, 陈启江, 等. 经食道降温对猪复苏后肺损伤及全身性炎症反应的影响[J]. 华西医学, 2019, 34: 1261-1267. https://www.cnki.com.cn/Article/CJFDTOTAL-HXYX201911009.htm
    [21]
    原志芳, 孙鑫, 孟月, 等. 青蒿琥酯治疗重症疟疾随机对照试验的系统评价[J]. 中国循证医学杂志, 2007, 7: 794-801. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ200711011.htm
    [22]
    Roberts BW, Kilgannon JH, Chansky ME, et al. Multiple organ dysfunction after return of spontaneous circulation in postcardiac arrest syndrome[J]. Crit Care Med, 2013, 41: 1492-1501. DOI: 10.1097/CCM.0b013e31828a39e9
    [23]
    Adrie C, Adib-Conquy M, Laurent I, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome[J]. Circulation, 2002, 106: 562-568. DOI: 10.1161/01.CIR.0000023891.80661.AD
    [24]
    Wei J, Wang P, Li Y, et al. Inhibition of RHO kinase by fasudil attenuates ischemic lung injury after cardiac arrest in rats[J]. Shock, 2018, 50: 706-713. DOI: 10.1097/SHK.0000000000001097
    [25]
    Wang Z, Wu L, Xu J, et al. Limb ischemic postconditioning alleviates postcardiac arrest syndrome through the inhibition of mitochondrial permeability transition pore opening in a porcine model[J]. Biomed Res Int, 2020, 2020: 9136097. http://pubmed.ncbi.nlm.nih.gov/32382579/
    [26]
    Shih CP, Kuo CY, Lin YY, et al. Inhibition of cochlear HMGB1 expression attenuates oxidative stress and inflammation in an experimental murine model of noise-induced hearing loss[J]. Cells, 2021, 10: 810. DOI: 10.3390/cells10040810
    [27]
    Qiu C, Yang LD, Yu W, et al. Paeonol ameliorates CFA-induced inflammatory pain by inhibiting HMGB1/TLR4/NF-κB p65 pathway[J]. Metab Brain Dis, 2021, 36: 273-283. DOI: 10.1007/s11011-020-00645-9
    [28]
    Shi X, Li M, Huang K, et al. HMGB1 binding heptamer peptide improves survival and ameliorates brain injury in rats after cardiac arrest and cardiopulmonary resuscitation[J]. Neuroscience, 2017, 360: 128-138. http://download.xuebalib.com/79ppvEMRrZC.pdf
    [29]
    Sugita A, Kinoshita K, Sakurai A, et al. Systemic impact on secondary brain aggravation due to ischemia/reperfusion injury in post-cardiac arrest syndrome: a prospective observational study using high-mobility group box 1 protein[J]. Crit Care, 2017, 21: 247. DOI: 10.1186/s13054-017-1828-5
    [30]
    Wang L, Li R, Guan X, et al. The value of extracellular cold-inducible RNA-binding protein (eCIRP) in predicting the severity and prognosis of patients after cardiac arrest: A preliminary observational study[J]. Shock, 2021, 56: 229-236.
    [31]
    Hao D, Wang Y, Yang J, et al. The alleviation of LPS-induced murine acute lung injury by GSH-mediated PEGylated artesunate prodrugs[J]. Front Pharmacol, 2022, 13: 860492.
    [32]
    Cui Y, Weng W, Ding Q, et al. The protective effect of artesunate on LPS-induced acute respiratory distress syndrome through inhibiting NLRP3 inflammasome signaling[J]. Evid Based Complement Alternat Med, 2022, 2022: 7655033. http://pubmed.ncbi.nlm.nih.gov/36051498/
    • Related Articles

  • Related Articles

    [1]WANG Caihong, LIU Rongxin, TANG Feng, WEI Xiaotao, XU Ziqing, HOU Huaijing, ZHANG Jie, ZHAO Yongqiang, XUE Jianjun. Research Progress on the Role of NLRP3 Inflammasome and Microglia in Cognitive Impairment[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(6): 1282-1288. DOI: 10.12290/xhyxzz.2023-0217
    [2]LIU Huan, HUANG Xiaoling, DAI Mengying, GUO Jiejie, GAO feng. Clinical Characteristics and Inflammatory Markers of Omicron BA.5.2 Variant Infection in Hospitalized Patients and Their Predictive Role in Disease Prognosis[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 1038-1045. DOI: 10.12290/xhyxzz.2023-0055
    [3]CAO Jun, QIN Jinmei, XUE Weizhen. Recent Advances in the Pathogenesis of Coronary Microvascular Disease: The role of Inflammatory Reactions[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(6): 1057-1063. DOI: 10.12290/xhyxzz.2021-0782
    [4]LIU Yuan, ZHAO Lin. Update and Interpretation of 2022 National Comprehensive Cancer Network Clinical Practice Guidelines for Gastric Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(6): 999-1004. DOI: 10.12290/xhyxzz.2022-0271
    [5]ZHANG Xi, HUANG Bing, WANG Guipeng. Progress of NLRP3 Inflammasome and Myocardial Ischemia Reperfusion Injury[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(2): 296-301. DOI: 10.12290/xhyxzz.2021-0619
    [6]Jia-qi ZHANG, Lei LIU, Gui-ge WANG, Wen-liang BAI, Shan-qing LI. Clinical Pathological Features and Prognosis of Non-small Cell Lung Cancer with Skip N2 Lymph Node Metastasis[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(3): 272-277. DOI: 10.3969/j.issn.1674-9081.2019.03.015
    [9]Ming-sheng MA, Xü-de ZHANG, Min WEI, Shi-min ZHAO, Zheng-qing QIU. Efficacy of Low Dose Corticosteroid Therapy in Duchenne Muscular Dystrophy[J]. Medical Journal of Peking Union Medical College Hospital, 2014, 5(4): 384-388. DOI: 10.3969/j.issn.1674-9081.2014.04.006
    [10]Shuai TANG, Jie YI, Yu-guang HUANG. Cardiovascular Responses of Intubation with Shikani Seeing Optical Stylet and Macintosh Laryngoscope[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(3): 314-317. DOI: 10.3969/j.issn.1674-9081.2012.03.015

  • Cited by

    Periodical cited type(3)

    1. 王晓宁，孙家安，王燕，段浩朋. 血清CitH3、PCT及IL-10检测对体外心肺复苏后急性肺损伤的预测价值. 西南医科大学学报. 2025(01): 58-62 .
    2. 潘蕊，乔秋杰，曾江楠，叶廷林，罗瑞琪，刘玉. 基于JAK2-STAT3信号通路探讨热毒宁注射液治疗大鼠急性肺损伤的作用机制. 陕西中医. 2024(08): 1021-1025 .
    3. 白媛媛，王变利，张会敏，闫雪生. 青蒿在猪养殖业中的研究进展. 粮食与饲料工业. 2024(05): 60-62+75 .

    Other cited types(0)

Catalog

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (1731) PDF downloads (63) Cited by(3)
    Related
    Links: National Health Commission of the People's Republic of China Chinese Academy of Medical Sciences(CAMS) AMLC Check CNKI Database CNKI Term Online Chinese General Practice
    Address：Room 302,Third Floor,Building 7, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, China
    Tel：010-69154261/4262
    E - mail：medj@pumch.cn mjpumch@126.com
    Copyright of website：Editorial Office of Medical Journal of Peking Union Medical College Hospital

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return
    x Close Forever Close