Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats.

Autor: Zhou J; Department of Anesthesia, Dalhousie University, 5850 College St., Halifax, B3H 4R2 Nova Scotia, Canada; Department of Microbiology & Immunology, Dalhousie University, 5850 College St., Halifax, B3H 4R2 Nova Scotia, Canada., Soltow M; Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-University, Loefflerstr. 23, 17475 Greifswald, Germany., Zimmermann K; Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-University, Loefflerstr. 23, 17475 Greifswald, Germany., Pavlovic D; Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-University, Loefflerstr. 23, 17475 Greifswald, Germany., Johnston B; Department of Microbiology & Immunology, Dalhousie University, 5850 College St., Halifax, B3H 4R2 Nova Scotia, Canada., Lehmann C; Department of Anesthesia, Dalhousie University, 5850 College St., Halifax, B3H 4R2 Nova Scotia, Canada; Department of Microbiology & Immunology, Dalhousie University, 5850 College St., Halifax, B3H 4R2 Nova Scotia, Canada. Electronic address: chlehmann@mac.com.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2015 Sep; Vol. 101, pp. 33-7. Date of Electronic Publication: 2015 Jun 24.
DOI: 10.1016/j.mvr.2015.06.004
Abstrakt: Introduction: Toll like receptor 4 (TLR4) represents a critical cellular link for endotoxin-induced pathology. The aim of this study was to evaluate the potential role of TLR4 inhibition on the intestinal microcirculation during experimental endotoxemia.
Materials and Methods: The intestinal microcirculation was studied by intravital microscopy in four groups of Lewis rats (n=10 per group): healthy controls (CON group), endotoxemic animals (15mg/kg lipopolysaccharide, LPS group), endotoxemic animals treated with a TLR4 antagonist (1mg/kg CRX-526, LPS+CRX526 group), and controls treated with CRX-526 (C-CRX526 group). Plasma samples were obtained for cytokine measurements at the end of the experiments.
Results: Endotoxemia significantly increased leukocyte adhesion in intestinal submucosal venules (e.g., V1 venules: CON 20.4±6.5n/mm(2), LPS 237.5±36.2n/mm(2), p<0.05) and reduced capillary perfusion of the intestinal wall (e.g., longitudinal muscular layer: CON 112.5±5.9cm/cm(2), LPS 71.3±11.0cm/cm(2), p<0.05) at 2h. TLR4 inhibition significantly reduced endotoxemia-associated leukocyte adhesion (V1 venules: 104.3±7.8n/mm(2)) and improved capillary perfusion (longitudinal muscular layer: 111.0±12.3cm/cm(2)). Cytokine release was not significantly affected.
Conclusions: The TLR4 pathway may be a target in clinical Gram-negative sepsis since administration of the TLR4 antagonist CRX-526 improved intestinal microcirculation parameters in experimental endotoxemia.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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