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Sepsis is due to blood bacteria or bacteria within the lesion to release a lot of endotoxin to the blood, or enter many endotoxin-contaminated liquid caused by a pathophysiological manifestation. Endotoxin is divided into two categories: endogenous and exogenous. The clinical symptoms of sepsis are mainly determined by the host’s resistance to endotoxin. Symptoms and signs are: fever, changes in white blood cell count, bleeding tendency, heart failure, renal dysfunction, liver damage, nervous system symptoms, and shock.
HMGB1 is thought to be a key late proinflammatory mediator of sepsis, based on the unique secretory mode of HMGB1 and its lethal effect in sepsis. Preventing HMGB1 from releasing or inhibiting the proinflammatory activity of HMGB1 has become a hotspot in the potential treatment strategy of sepsis.
Research results show that the application of HMGB1 polyclonal antibody passive immunization of mice, mice can be prevented from death caused by sepsis. Even after 2 h of lipopolysaccharide infection, HMGB1 still has a significant therapeutic effect. HMGB1 polyclonal antibody neutralization effect was dose-dependent. A variety of drugs can inhibit macrophages and monocytes to release HMGB1. Glycerol and Lactose Derivative Gu-4 can inhibit the release of HMGB1 by macrophages and inhibit the activity of HMGB1 by inhibiting cecal ligation and puncture (CLP), which can significantly improve CLP-induced sepsis model animal survival rate.
In the case of liver injury and acute liver failure (FHF), liver clearance endotoxin function was reduced. When FHF happens, sepsis incidence could be up to 90-100%, which has a significant role on increasing liver failure and inducing multiple organ dysfunction. Previous studies have focused on cytokine TNF, IL-1, IL-6, NO and so on. HMGB1 as a newly discovered cell medium is predominantly stimulated by macrophages active secretion. The liver has many macrophages exists. FHF and often complicated by sepsis. Therefore, it can be inferred that HMGB1 is involved in the pathophysiological process of liver injury in acute liver failure and may play an important role. But the changes of HMGB1 in liver tissue and blood before and after acute liver failure and its relationship with injury have not been reported. HMGB1 not only has its own cytokine-like effect, but also induced macrophages and neutrophils produce a variety of inflammation.
At present, about HMGB1 as a new late inflammatory mediator are still in the early stages of research. The mechanism needs to be studied further. For example, what is the release mechanism of HMGB1? What is the mechanism of inflammatory cell activation of detailed signal transduction and molecular signaling? In addition to RAGE whether there are other HMGB1 specific receptor anti-HMGB1 antibody? HMGB1 has a protective effect on the animal infection model. Can we use anti-HMGB1 antibody to treat sepsis?
WangH, BloomO, ZhangM, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science,1999,285(5425):248–251.
HMGB1 was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure.
SeoES, OhBK, PakJH, et al. Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release. Mol Cells, 2013,35(4):348–354.
In vitro, acteoside inhibits high mobility group box 1 (HMGB1) release and iNOS/NO production and induces heme oxygenase-1 (HO-1) expression in a concentration-dependent manner, while HO-1 siRNA antagonizes the inhibition of HMGB1 and NO. In vivo, acteoside increases survival and decreases serum and lung HMGB1 levels in CLP-induced sepsis. Overall, these results that acteoside reduces HMGB1 release and may be beneficial for the treatment of sepsis.