title: Unfractionated heparin attenuates intestinal injury in mouse model of sepsis by inhibiting heparanase.
abstract: Intestinal injury is a key feature in sepsis. Heparanase, a heparin sulfate-specific glucuronidase, mediates the onset of organ injury during early sepsis. Heparin has the function to attenuate inflammation and injury induced by multiple factors; however, whether unfractionated heparin (UFH) can attenuate the intestinal injury induced by sepsis as well as the underlying mechanism is still unknown. In the present study, the function of UFH in intestinal injury induced by sepsis was explored. Results of our study showed that after CLP operation, the inflammatory response and expression of heparanase were increased and NF-κB and MAPK P38 signaling pathways were activated. However, pretreatment with UFH will inhibit the expression and activation of heparanase, and reverse the activation of NF-κB and MAPK P38 signaling pathways, thus attenuating inflammatory responses induced by sepsis. These results suggest that UFH may be a promising therapeutic drug for intestinal injury caused by sepsis.
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002432:Cecum / Q000382:microbiology / Q000601:surgery; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011677:Punctures; D018805:Sepsis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099175:Heparanase
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D006493:Heparin; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D000099175:Heparanase
keywords: MAPK; NF-κB; Unfractionated heparin; heparanase; intestinal injury; sepsis