| Background Sepsis is a systemic inflammatory response syndrome caused by infection, its mechanism is extremely complex, cell wall components released by the bacterial infection such as lipopolysaccharide, lipid peptide cause sustained activation of host cells which results in over-production and over-release of inflammatory mediators followed by the occurrence of excessive inflammatory response leading to cell and tissue damage, and even organ failure. Organ dysfunction caused by sepsis happens with relative regularity, for example, liver damage occurs earlier and has a higher frequency of damage. Therefore, early prevention of liver injury in sepsis treatment has great significance for the treatment to reduce morbidity and mortality caused by sepsis. VIP is a28-amino acid peptide with a variety of biological functions. VIP can be synthesized and released by immune cells and play an immunomodulatory role by regulating the balance between pro-inflammatory and anti-inflammatory cytokines, also it can induce the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors. Therefore, we believe that VIP may play an important role in both the treatment of sepsis and prevention of liver damage occurring in the same process.Objective Study the effect of VIP on liver injury in septic rats and its possible mechanismMethod In our project, a sepsis model by cecal ligation and puncture (CLP) in rats was made and VIP treatment was followed, enzyme-linked immunosorbent assay (ELISA) were used to detect serum levels of tumor necrosis factor-α (TNF-alpha), interleukin-10(IL-10), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) pre-or post-VIP treatment at different time points. Also the morphological changes of rat liver were observed to explore the role of VIP on liver injury in septic rats.Results1. After CLP treatment, the serum levels of inflammatory cytokines TNF-a, IL-10and serum hepatic parameters ALT, AST were significantly elevated and liver pathological damage was obvious. CLP rats had sepsis symptoms and survival rate of CLP rats was significantly lower than that of rats with sham operation. These suggested that the sepsis rat model is successful.2. VIP treatment relieved the symptoms of septic rats. The survival rate was significantly higher than the NS group. At6h,12h and24h time point the levels of pro-inflammatory cytokines TNF-a was significantly lower than NS group, while levels of the anti-inflammatory cytokines IL-10was significantly higher than the NS group. At12h,24h time point the levels of ALT, AST decreased significantly compared with NS group, indicating that VIP can inhibit the release of pro-inflammatory factors, promote the release of anti-inflammatory cytokine and has a protective effect on the liver.Conclusions1. VIP can reduce the pathological damage of the liver and improve the survival rate of CLP rats.2. VIP may play a protective role by inhibiting the generation of pro-inflammatory cytokines and promoting the production of anti-inflammatory cytokines. This study provides new experimental evidence and research ideas for the use of VIP in clinical treatment of sepsis. |
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