title: Unfractionated heparin ameliorates lipopolysaccharide-induced lung inflammation by downregulating nuclear factor-κB signaling pathway.
abstract: The present study aimed to determine the protective effects and the underlying mechanisms of unfractionated heparin on lipopolysaccharide (LPS)-induced endotoxemia and lung injury in rats. Rats were injected intravenously with LPS at 6 mg/kg. We examined the therapeutic effects of unfractionated heparin (100 or 300 U/kg) on LPS-induced endotoxemia by dosing intravenously simultaneously after LPS challenge. The animal lung edema degree was evaluated by wet/dry weight ratio. The levels of inflammatory mediators including interleukin-1β (IL-1β) and interleukin-6 (IL-6) were assayed by enzyme-linked immunosorbent assay and quantitative real-time RT-PCR. The activation of nuclear factor-κB (NF-κB) was evaluated by Western blotting. The investigations revealed that treatment with unfractionated heparin can attenuate inflammatory responses in a rat model of LPS-induced acute lung injury, and the effect was much better in 300 U/kg group. The mechanisms by which unfractionated heparin exerts its anti-inflammatory effect are correlated with inhibition of IL-1β and IL-6 production via inactivation of NF-κB.
authors.affiliation: Department of Intensive Care Unit, the First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang, 110001, Liaoning Province, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yina
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D015536:Down-Regulation; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy; D006493:Heparin / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D006493:Heparin