3.1 Imbalance of inflammatory response
When pathogenic microorganisms and virulence factors invade the body,
the body activates the innate immune system through a series of
inflammatory reactions to resist pathogen infection. However, when the
inflammatory reaction is over-activated, it will cause organ dysfunction
and further aggravate the injury. Inflammatory cytokines play an
important role in the progression of sepsis and are involved in multiple
organ injury in sepsis. At present, most scholars believe that the
pro-inflammatory factor TNF- α is not only the ”core factor” causing
dysfunction and injury of many important organs, but also the initiating
factor, and is closely related to IL-1β Play a synergistic effect[24]. IL- 1β As another key inflammatory factor,
studies have found that inhibition of IL-1β Expression can reduce
hemodynamic and metabolic disorders in severe sepsis[25]. In addition, IL-1β Can promote monocyte
chemoattractant protein-1, I-κBα. The synthesis of multiple inflammatory
genes, such as MKP-1 and other interleukin-like cytokines, further
promotes the spread of inflammatory reaction and causes sepsis-related
organ dysfunction[26]. During lipopolysaccharide
LPS-induced sepsis, HMGB1 can cause multiple tissue and organ damage
through different mechanisms, such as lung, kidney, liver,
cardiovascular, and nervous systems[27].
Fu[28] and other researchers believe that HMGB1 is
over-regulated in sepsis, and experiments have confirmed that HMGB1 has
a protective effect on septic liver injury by targeting HMGB1. When
cells are stimulated by pathogenic microorganisms and bacterial
products, nuclear factor κ B (NF- κ B) Nuclear translocation and its
promoter will be activated, leading to the release of pro-inflammatory
factors, including TNF- α、IL-1β. At the same time, these inflammatory
factors will further positively feedback and activate NF- κ B. Lead to
the imbalance of inflammatory response and then aggravate sepsis.