title: Inhibition of Na+/H+ exchanger 1 by cariporide reduces burn-induced intestinal barrier breakdown.
abstract: Severe burns initiate an inflammatory cascade within the gut, which leads to intestinal mucosal injury. Although Na(+)/H(+) exchanger 1 (NHE1) is recognised as a pivotal player in several inflammatory processes, its role in burn-induced intestinal injury is relatively unknown. We hypothesised that NHE1 might be involved in the increased intestinal permeability and barrier breakdown after severe burns. Thus, we here investigate whether the inhibition of NHE1 has a protective effect on burn-induced intestinal injury. Mice were subjected to a 30% total body surface area (TBSA) full-thickness steam burn. Cariporide was used to assess the function of NHE1 in mice with burn-induced intestinal injury by fluorescence spectrophotometry, Western blotting and enzyme linked immunosorbent assay (ELISA). We found that severe burn increased intestinal permeability, associated with the up-regulation of NHE1 and raised inflammatory cytokine levels. Mice treated with the NHE1 inhibitor cariporide had significantly attenuated burn-induced intestinal permeability and a reduced inflammatory response. NHE1 inhibition also reduced nuclear factor-κB (NF-κB) activation and attenuated p38 mitogen-activated protein kinase (MAPK) phosphorylation. Our study suggests that NHE1 plays an important role in burn-induced intestinal permeability through the regulation of the inflammatory response. Inhibition of NHE1 may be adopted as a potential therapeutic strategy for attenuating intestinal barrier breakdown.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shannxi 710032, People's Republic of China.
authors.forename: Xuekang
authors.initials: X
authors.lastname: Yang
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Hongyi
authors.initials: H
authors.lastname: Hou
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D016328:NF-kappa B; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Burns; Inflammation; Na(+)/H(+) exchanger 1; Small intestine