Calcitonin gene-related peptide mediates delayed preconditioning of monophosphoryl lipid A by decreasing tumor necrosis factor α in rat small intestine

AIM: To explore whether monophosphoryl lipid A participates in the protective process of the delayed ischemic preconditioning in the small intestine of rats,and whether endogenous calcitonin gene-related peptide and tumor necrosis factor α are mediators in this process.METHODS: Intestinal ischemia was induced by occlusion of super mesenteric artery for 30 min,followed by reperfusion for 60 min.The ischemia/reperfusion(I/R) injury was made by 1 h ischemia and 15 min reperfusion in situ perfusion in rat small intestine.The intestine lesions were evaluated by the measurement of serum lactate dehydrogenase and malondialdehyde in the small intestinal tissues.In addition,calcitonin gene-related peptide and tumor necrosis factor α in plasma and superior mesenteric vein effluent were also examined.RESULTS: Pretreatment with monophosphoryl lipid A(500 μg/kg,ip) 24 h prior to I/R significantly alleviated the histolo-gical lesions of intestinal tissues,decreased serum level of lactate dehydrogenase and reduced the tissue content of malondialdehyde.Moreover,monophosphoryl lipid A markedly increased plasma concentrations of calcitonin gene-related peptide and decreased plasma concentrations of tumor necrosis factor α.Pretreatment with capasicin,which specifically depletes the neurotransmitter content of sensory nerves,or calcitonin gene-related peptide(8-37),a selective calcitonin gene-related peptide receptor antagonist,inhibited the increase in calcitonin gene-related peptide release and subsequently abrogated the protective effect of monophosphoryl lipid A.CONCLUSION: Monophosphoryl lipid A pharmacologically mimics delayed preconditioning,which may be related to the stimulation of calcitonin gene-related peptide release and inhibition of tumor necrosis factor α production in rat small intestine.