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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01320

Post-treatment with QING-YING-TANG, A Chinese Medicine Formula, Ameliorates Lipopolysaccharide Induced Cerebral Microcirculation Disturbance in Mice

Hao-Min Wang1, Ping Huang2, Quan Li2, Kai Sun2,  Li Yan2,  Chun-Shui Pan2,  Xiao-Hong Wei2, Yu-Ying Liu2, Bai-He Hu2, Chuan-She Wang1, Jing-Yu Fan2 and  Jing-Yan Han1*
  • 1Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, China
  • 2Tasly Microcirculation Research Center, Peking University Health Science Center, China

Objective: Lipopolysaccharide (LPS) causes microvascular dysfunction, which plays a key role in the development of endotoxemia. The present study aimed to investigate the efficacy of QING-YING-TANG (QYT), a traditional Chinese formula in cerebral microcirculation disturbance and brain injury induced by LPS.
Methods: Male C57/BL6 mice were continuously infused with LPS (7.5mg/kg/h) via the left femoral vein for 2 hours. QYT (14.3g/kg) was given by gavage 2 hours 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 tight junction protein. This result suggests QYT as a potential strategy to deal with endotoxemia.

Keywords: leukocyte, Hyperpermeability, NF-κB, src, Tight Junctions, caveolin-1

Received: 15 May 2019; Accepted: 01 Oct 2019.

Copyright: © 2019 Wang, Huang, Li, Sun, Yan, Pan, Wei, Liu, Hu, Wang, Fan and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jing-Yan Han, Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, Beijing, China, hanjingyan@bjmu.edu.cn