Monophosphoryl Lipid A-Induced Delayed Preconditioning in Rat Small Intestine Is Mediated by Calcitonin Gene-Related Peptide

Author： Yang Cai-Hong Zhang Ming-Sheng Li Jie Zhang Xuan-Ping Wang Hang Hao Yi-Bin

Publisher： Springer Publishing Company

ISSN： 0163-2116

Source： Digestive Diseases and Sciences, Vol.56, Iss.5, 2011-05, pp. : 1333-1341

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Abstract

Protective effects of ischemic preconditioning in rat small intestine have been shown to be related to the release of calcitonin gene-related peptide.The purpose of the present study was to explore whether monophosphoryl lipid A participated in the protective process of the delayed ischemic preconditioning in the peripheral vascular bed (the anse intestinalis of rat), and whether endogenous calcitonin gene-related peptide is a mediator in this process.Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 30 min, followed by reperfusion for 60 min. The intestinal lesions were evaluated by the measurement of serum lactate dehydrogenase, myeloperoxidase levels, and small intestine tissue contents of malondialdehyde. In addition, calcitonin gene-related peptide in plasma and superior mesenteric vein effluent were also examined.Pretreatment with monophosphoryl lipid A (500 μg/kg. i.p.) 24 h prior to ischemia–reperfusion significantly alleviated the intestinal tissue histology lesions, decreased serum levels of lactate dehydrogenase, myeloperoxidase, and reduced tissue content of malondialdehyde. Moreover, monophosphoryl lipid A markedly increased plasma concentrations of calcitonin gene-related peptide. Pretreatment with capsaicin, 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 increased calcitonin gene-related peptide release and subsequently abrogated the protection by monophosphoryl lipid A.In conclusion, monophosphoryl lipid A pharmacologically mimics delayed preconditioning and the protective effects are related to the stimulation of calcitonin gene-related peptide release in rat small intestine.