Inhibition of spleen tyrosine kinase as treatment of postoperative ileus

摘要: Objective Intestinal inflammation resulting from manipulation-induced mast cell activation is a crucial mechanism in the pathophysiology of postoperative ileus (POI). Recently it has been shown that spleen tyrosine kinase (Syk) involved degranulation. Therefore, we have evaluated effect Syk-inhibitor GSK compound 143 (GSK143) as potential treatment to shorten POI. Design In vivo: mouse model POI, Syk inhibitor was on gastrointestinal transit, muscular and cytokine production. vitro: GSK143 doxantrazole were cultured peritoneal cells (PMCs) bone marrow derived macrophages. Results intestinal manipulation resulted delay transit at t=24 h (Geometric Center (GC): 4.4±0.3). Doxantrazole significantly increased (GC (10 mg/kg): 7.2±0.7; (1 mg/kg): 7.6±0.6), reduced prevented recruitment immune muscularis. PMCs, substance P (0–90 μM) trinitrophenyl (0–4 μg/ml) induced concentration-dependent release β-hexosaminidase. Pretreatment with (0.03–10 μM) concentration dependently blocked β-hexosaminidase release. addition, able reduce expression endotoxin-treated macrophages manner. Conclusions The reduces macrophage degranulation vitro. inhibits restores mice. These findings suggest inhibition may be new tool