Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation

作者全名："Yili, Sun; Xinyi, Dai; Kerui, Fan; Kun, Chen; Yang, Yongqiang; Zhang, Li; Hu, Kai"

作者地址："[Yili, Sun; Xinyi, Dai; Kerui, Fan; Kun, Chen; Yang, Yongqiang; Zhang, Li] Chongqing Med Univ, Dept Pathophysiol, Chongqing, Peoples R China; [Hu, Kai] Chongqing Med Univ, Dept Histol & Embryol, Chongqing, Peoples R China; [Zhang, Li] Chongqing Med Univ, Basic Coll, Dept Pathophysiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Hu, Kai] Chongqing Med Univ, Basic Coll, Dept Histol & Embryol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Zhang, L (通讯作者)，Chongqing Med Univ, Basic Coll, Dept Pathophysiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Hu, K (通讯作者)，Chongqing Med Univ, Basic Coll, Dept Histol & Embryol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001064841100001

JCR分区：Q2

影响因子：3

年份：2023

卷号：37

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：intestinal ischemia/reperfusion; neutrophil extracellular traps; acute lung injury; inflammation; GPR81

摘要："IntroductionIntestinal ischemia/reperfusion (II/R) injury is a life-threatening situation accompanied by severe organ injury, especially acute lung injury (ALI). A great body of evidence indicates that II/R injury is usually associated with hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, has been recognized as a regulatory factor in inflammation, but whether it was involved in II/R injury-induced ALI is still unknown.MethodsTo establish the II/R injury model, the superior mesenteric artery of the mice was occluded gently by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the lung injury after II/R. The pulmonary histopathological alteration was evaluated by H & E staining. The concentration of proteins, the number of infiltrated cells, and the level of IL-6 were measured in BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme linked immunosorbent assay (ELISA).ResultsAdministration of the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological abnormalities, upregulated the concentration of proteins, the number of infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma.ConclusionAfter induction of ALI by II/R, the administration of DHBA aggravated ALI through NETs formation in the lung."

基金机构："Natural Science Foundation of Chongqing, China [cstc2021jcyj-msxmX0197]"

基金资助正文："The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is sponsored by Natural Science Foundation of Chongqing, China. Grant/Award Numbers: cstc2021jcyj-msxmX0197."