Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 14, Issue 3, Pages 243-251Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2012.07.010
Keywords
Rhynchophylline; Lipopolysaccharide; Mice; Myocardial dysfunction; Inhibitor-kappa B alpha
Categories
Funding
- National Natural Science Foundation of China [30670826, 81170222]
- Leading Academic Discipline Program
- 211 Project for Jinan University
- Foundation of Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China
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Myocardial dysfunction is a common complication during sepsis and significantly contributes to the mortality of patients with septic shock. However, none of the available therapeutic strategies proven to be effective in patients with severe sepsis are designed specifically to target myocardial dysfunction. The purpose of the present study is to investigate the effect of rhynchophylline (Rhy) on LPS-induced myocardial dysfunction in mice. We found that pretreatment with Rhy significantly improved cardiac systolic dysfunction, increased stroke volume and cardiac output in mice challenged with LPS. LPS induced cardiac inhibitor-kappa B alpha (I-kappa B alpha) phosphorylation, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) mRNA expression, and in turn increased cardiac TNF-alpha and IL-1 beta protein production, all of which were attenuated by pretreatment with Rhy. Immunohistochemistry revealed that TNF-alpha was found in infiltrated macrophages (F4/80(+)) and myocardium, and Rhy reduced TNF-alpha immunostaining in cardiac infiltrated macrophages in LPS-challenged mice. Furthermore, Rhy inhibited LPS-induced I-kappa B alpha phosphorylation and TNF-alpha production in cultured mouse peritoneal macrophages, but not in neonatal mouse cardiomyocytes. Pretreatment with Rhy significantly decreased the mortality of LPS-challenged mice. These results indicate that Rhy reduces cardiac dysfunction and improves survival via suppression of macrophage I-kappa B alpha phosphorylation in LPS-challenged mice, and suggest that Rhy may be a potential agent for the treatment of septic cardiac dysfunction. (C) 2012 Elsevier B.V. All rights reserved.
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