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Post‐treatment With Qing‐Ying‐Tang, a Compound Chinese Medicine Relives Lipopolysaccharide‐Induced Cerebral Microcirculation Disturbance in Mice
Author(s) -
Han Jingyan
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08900
Subject(s) - occludin , intravital microscopy , microcirculation , lipopolysaccharide , blood–brain barrier , medicine , western blot , paracellular transport , adherens junction , tight junction , neuroinflammation , pharmacology , pathology , transcellular , inflammation , immunology , chemistry , microbiology and biotechnology , cadherin , biology , central nervous system , biochemistry , cell , membrane , gene , permeability (electromagnetism)
Objective Lipopolysaccharide (LPS) causes microvascular dysfunction, which is a key episode in the pathogenesis of endotoxemia. This work aimed to investigate the effect of Qing‐Ying‐Tang (QYT), a compound Chinese medicine in cerebral microcirculation disturbance and brain damage induced by LPS. Methods Male C57/BL6 mice were continuously transfused with LPS (7.5 mg/kg/h) through the left femoral vein for 2 h. QYT (14.3 g/kg) was given orally 2 h after LPS administration. The dynamics of cerebral microcirculation were evaluated by intravital microscopy. Brain tissue edema was assessed by brain water content and Evans Blue leakage. Cytokines in plasma and brain were evaluated by flow cytometry. Confocal microscopy and Western blot were applied to detect the expression of junction and adhesion proteins, and signaling proteins concerned in mouse brain tissue. Results Post‐treatment with QYT significantly ameliorated LPS‐induced leukocyte adhesion to microvascular wall and albumin leakage from cerebral venules and brain tissue edema, attenuated the increase of MCP‐1, MIP‐1α, IL‐1α, IL‐6, and VCAM‐1 in brain tissue and the activation of NF‐κB and expression of MMP‐9 in brain. QYT ameliorated the downregulation of claudin‐5, occludin, JAM‐1, ZO‐1, collagen IV as well as the expression and phosphorylation of VE‐cadherin in mouse brain. Conclusions This study demonstrated that QYT protected cerebral microvascular barrier from disruption after LPS by acting on the transcellular pathway mediated by caveolae and paracellular pathway mediated by junction proteins. This result suggests QYT as a potential strategy to deal with endotoxemia.