We recently showed anti‐inflammatory role of cholinergic pathway (Ch.Path) in liver IR by pharmacological stimulation of acetylcholine receptor. Here we tested whether endogenous Ch.Path (e.Ch.Path) activation would exert a similar protective effect, and studied liver gene expression modulation by Ch.Path activation.MethodsMice treated with CCK‐8 or nicotine, i.p. prior to ischemia (CCK‐8 stimulates acetylcholine release via Ch.Path). A 2nd group was subjected to bilateral vagotomy prior to CCK‐8, while a 3rd group subjected to electrical vagal stimulation for 20min, followed by liver IR (90min I : 3h R). Plasma ALT and cytokines levels and liver histopathology were assessed.ResultsCCK‐8‐ or nicotine treatment significantly reduced liver injury (87%, and %69 respectively) and cytokine production, as compared to saline‐treated mice. CCK‐8 protective effect was absent in vagotomized mice, indicating e.Ch.Path role. Electrical vagal nerve stimulation confirmed the observation as ALT levels and liver injury were significantly decreased in this group. Gene array data showed significant modulation of several pathways and associated genes.Conclusionse.Ch.Path activation via humoral or electrical stimuli provides a protective effect on liver IR injury, which could offer therapeutic means to selectively act on targeted genes for treatment of IR inflammatory diseases. Support: NIH HL075475.
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