Protective Effect of Unfractionated Heparin on Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Neonatal Mice via the JAK2/STAT3 Signaling Pathway

作者全名："Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan"

作者地址："[Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan] Chongqing Med Univ, Childrens Hosp, Neonatal Diag & Treatment Ctr, Chongqing 400014, Peoples R China; [Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China; [Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan] Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China; [Xiong, Jing; Ai, Qing; Bao, Lei; Shi, Yuan] Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China"

通信作者："Shi, Y (通讯作者)，Chongqing Med Univ, Childrens Hosp, Neonatal Diag & Treatment Ctr, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China."

来源：FRONTIERS IN BIOSCIENCE-LANDMARK

ESI学科分类：　

WOS号：WOS:001025471300001

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：28

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：acute respiratory distress syndrome; unfractionated heparin; JAK2; STAT3 pathway; mice; newborn

摘要："Background: Neonatal acute respiratory distress syndrome (ARDS) is a clinical disorder characterized by excessive acute inflammatory response in lung parenchyma and has high morbidity and mortality. However, the therapeutic treatments are still lacking. The aim of this study is to evaluate the role of unfractionated heparin in neonatal ARDS and explore the underlying mechanism of its effects. Methods: To conduct the ARDS model, the mouse pups were treated by intraperitoneal injection of lipopolysaccharide (LPS) (10 mg/kg). For unfractionated heparin intervention group, C57BL/6 mouse pups received a single subcutaneous injection of unfractionated heparin (400 IU/kg) 30 minutes prior to LPS. The survival rate was recorded for each group. Histological analysis was used to evaluate lung injury. MPO (myeloperoxidase) concentration level in lung tissues and extracellular histones in serum were detected by enzyme linked immunosorbent assay (ELISA). A commercially available kit was used to detect inflammatory cytokine levels in serum. Real time quantitative polymerase chain reaction (qPCR) and western blot were used to detect the mRNA and protein in the JAK2/STAT3 signaling pathway, respectively. Results: Intervention of unfractionated heparin significantly increased the survival rate of mouse pups with ARDS, restored lung architecture, inhibited neutrophil infiltration as evidenced by reduced MPO concentration, and attenuated the LPS-induced inflammatory responses, characterized by the down-regulation of proinflammatoy factors and up-regulation of anti-inflammatory factor when compared with the ARDS group. In addition, the concentration of extracellular histones, which have been proven to be mediated in the pathogenesis of ARDS, was diminished by unfractionated heparin. Moreover, the protein expressions of p-JAK2 (Y1007/1008) and p-STAT3 (Y705) in the ARDS group were remarkably up-regulated, which were reversed by unfractionated heparin. Conclusions: Unfractionated heparin protects LPS-induced ARDS via inhibiting JAK2/STAT3 pathway in neonatal mice, which might present a novel therapeutic target for ARDS of neonates."

基金机构："National Clinical Research Center for Child Health and Disorders (Republic of China) [NCRCCHD-2020-GP-03]; Ministry of Science and Technology (Republic of China, Chongqing) [CSTC2021jscx-gksb-N0015]"

基金资助正文："This study was supported by grants of NCRCCHD-2020-GP-03 from the National Clinical Research Center for Child Health and Disorders (Republic of China, Chongqing) and CSTC2021jscx-gksb-N0015 from the Ministry of Science and Technology (Republic of China, Chongqing)."