OBJECTIVETo establish a model of systemic inflammatory response syndrome (SIRS) in rats.

METHODSSD rats were intraperitoneally injected with different concentrations of zymosan suspension. The general status, temperature, white cell count, tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-10 (IL-10) and the pathological changes of main organs were examined.

RESULTSThe conditions of rats receiving zymosan doses of 750 mg/kg and 1000 mg/kg were consistent with the criteria of SIRS model; however, the mortality of 1000 mg/kg group was higher than that of 750 mg/kg group.

CONCLUSIONThe rat model of systemic inflammatory response syndrome has been successfully induced.

Animals ; Disease Models, Animal ; Female ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Male ; Paraffin ; toxicity ; Rats ; Rats, Sprague-Dawley ; Systemic Inflammatory Response Syndrome ; blood ; chemically induced ; pathology ; Tumor Necrosis Factor-alpha ; blood ; Viscera ; pathology ; Zymosan ; toxicity

Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47 PHOX. Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47 PHOX may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.
Animals ; Cell Line ; Cell Membrane ; Cytosol ; Enzyme Inhibitors/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Macrophage-1 Antigen/pharmacology ; Macrophages/drug effects/*metabolism/ultrastructure ; Mice ; Myosin-Light-Chain Kinase/metabolism ; Opsonin Proteins/blood/*metabolism ; *Phagocytosis ; Protein Transport ; Protein-Serine-Threonine Kinases/metabolism ; Research Support, Non-U.S. Gov't ; *Signal Transduction ; Superoxides/*metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Zymosan/*blood ; p38 Mitogen-Activated Protein Kinases/metabolism ; rhoA GTP-Binding Protein/antagonists & inhibitors/*metabolism