Pediatric Critical Care Medicine:
May 2014 - Volume 15 - Issue 4_suppl - p 179
Effect Of Inhibiting Histone With Low-Dose Heparin On The Expression Of Toll-Like Receptor And Generation Of Inflammatory Mediators In Huvec
Li, B.; Li, B.I.R.U.; Cao, Q.I.N.G.
Background and aims: Vascular endothelial cells (EC) injury is the key factor of sepsis which led to multiple organ dysfunction syndrome (MODS). Our previous work found that the concentration of histone was significantly higher in serum of sick children with sepsis and MODS. In addition, incubation of EC with the recombinant histones can induce apoptosis of EC.
Aims: Our study explored the molecular mechanisms of vascular endothelial cells injury induced by histone which was inhibited by heparin. Low-dose heparin is possible to intervene in the amplification reaction and terminate the reaction at the starting point.
Methods: Detecting the induction effect of extracellular histone on human umbilical vein endothelial cells (HUVEC) induced apoptosis and anti-apoptotic effects of heparin. Detection of the activation and antibody blocking of NF-κB signaling pathway with western blot.Observation of septic mice survival rates after injection of heparin. Explorating the function of the low-dose heparin for the treatment of clinical sepsis.
Results: The histone concentrations increased in serum from sepsis patients with MODS and positively correlated with the severity of disease. The percentage of apoptotic cells increased as the concentration of histone elevated. Histone activated the NF-κB signaling pathway via activation of Toll-like receptors. Heparin can inhibit the process of histone induced apoptosis. After injection of heparin, the survival rates of sepsis mice were increased significantly. Low-dose heparin treatment of sepsis can reduce mortality and improve prognosis.
Conclusions: Our results provide a theoretical basis for the low-dose heparin therapy and improvement of sepsis and survival rate.