Taxifolin ameliorates sepsis-induced lung capillary leak through inhibiting the JAK/STAT3 pathway

被引:14
|
作者
Shen, Mengwen [1 ]
Lin, Baibai [2 ]
Qian, Fenghua [1 ]
Zhao, Lei [1 ]
Xi, Yao [1 ]
Qian, Yiming [1 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Dept Emergency Med, Yueyang Hosp Integrated Tradit Chinese & Western, 110 Ganhe Rd, Shanghai 200437, Peoples R China
[2] Shanghai Baoshan Dist Hosp Integrated Tradit Chin, Dept Emergency Med, Shanghai, Peoples R China
关键词
taxifolin; lung capillary leak; sepsis; Th17/Treg balance; JAK/STAT3 signaling pathway; SEPTIC SHOCK; CELLS; MODEL; TH17; MORTALITY; BALANCE; STAT3; TREG;
D O I
10.15586/aei.v50i2.550
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: As a systemic inflammatory reaction, sepsis is associated with various organ dysfunctions. The capillary leakage and the imbalance between T helper 17 and regulatory T (Th17/Treg) cells are associated with sepsis-induced lung injury. Taxifolin (TXL) has been found to play a vital role in regulating this diverse disease. However, the detailed functioning and mechanism of TXL in regulating sepsis-induced lung capillary leak remain elusive. Methods: Balb/c mice were used to establish sepsis-induced lung injury model through administration of lipopolysaccharide (LPS). The structure of lung tissues was observed by using hematoxylin & eosin staining. Protein level and total cells in bronchoalveolar lavage fluid (BALF) were measured by bicinchoninic acid (BCA) protein assay kit and hematimetry assay, respectively. Quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were employed to detect the level of inflammatory cytokines. The content of Th17 and Treg cells were measured by flow cytometry analysis. Western blot assay was used to determine the protein level of retinoid-related orphan receptor-gamma t (ROR gamma t), Forkhead box P3 (Foxp3), Janus kinase 2 (JAK2), phospho(p)-JAK2, signal transducer and activator of transcription 3 (STAT3), and phospho(p)-STAT3. Results: Taxifolin effectively prolonged the survival period of sepsis mice and alleviated LPS-induced lung injury in a dose-dependent manner. Moreover, TXL reduced LPS-induced increase in protein levels and T cell content in BALF, and effectively restored the wet:dry ratio of lung tissue and tissue permeability. Treating with TXL notably inhibited the production of pro-inflammatory cytokines induced by sepsis and influenced the balance between Th17 and Treg cells. Furthermore, TXL treatment suppressed the activation of JAK/STAT3 signaling pathway in a dose-dependent manner. Conclusion: Our findings revealed that TXL alleviated sepsis-induced capillary leak in the lungs of mice by regulating JAK/STAT3 signaling pathway. (C) 2022 Codon Publications. Published by Codon Publications.
引用
收藏
页码:7 / 15
页数:9
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