AUTHOR=Wang Hao-Min , Huang Ping , Li Quan , Yan Lu-Lu , Sun Kai , Yan Li , Pan Chun-Shui , Wei Xiao-Hong , Liu Yu-Ying , Hu Bai-He , Wang Chuan-She , Fan Jing-Yu , Han Jing-Yan 

TITLE=Post-treatment With Qing-Ying-Tang, a Compound Chinese Medicine Relives Lipopolysaccharide-Induced Cerebral Microcirculation Disturbance in Mice

JOURNAL=Frontiers in Physiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.01320

DOI=10.3389/fphys.2019.01320

ISSN=1664-042X

ABSTRACT=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.