| ObjectiveThe aim of this article is to study the expression of cyclooxygenase-2 on hepatic inflammatory reaction of rats with sepsis and to evaluate the effect of NS-398 through in animal mode of cecal ligation and puncture(CLP) ,to explore a efficient methode of protecting hepatic cell, especially find out a new pathway of prevention and treatment of sepsis.Methods54 Wistar rats were to divided into 3 groups at random. Group A: shame group ; Group B: sepsis model group; Group C: NS-398 intervention group. All rats were underwent cecal ligation and puncture(CLP) or shame operation . RT-PCR were used to determine cyclooxygenase-2 mRNA expression, serum IL-6, TNF-αand IL-10 were detected by ELISA, percent of CD4+, CD8+ T cell subclassification were detected by flow cytometer, and the changes of NF-κB detected by immunohistochemical method. At the same time hepatic pathological changes and hepatic function were observed.Results1. The expression of cyclooxygenase-2 mRNA of hepatic tissue were lower on group A (1040.82±2.77), where it was obviously enhanced after CLP at 3h(2064.04±6.78) and peaked at 6h(3992.45±16.75). High expression were showed at 12h and 24h (2916.80±6.79 , 2237.80±7.42). In group C, it was lower than in group B at different time , but higher than in group A.2. In group B, IL-6 and IL-10 in serum obviously increased after CLP at 3h and peak value of IL-6, IL-10 were at 24h after CLP. It has statistical significance compared with Group A at the same time (P<0.01). But TNF-a in serum reached higher level after early CLP and had not statistical significance in this group(P>0.05).IL-6 were lower in group C than in group B at the same time, though it increased. It had statistical significance compared with B group at 12h and 24h. IL-10 in serum were higher in group C than in group A, B at the same time and has statistical significance(P<0.05). The changes of TNF-a had a tendency of degrade compared with group B, but no statistical significance(P>0.05).3. Ratios of CD4+/CD8+ in serum were decreased after CLP. To compared with group B, ratios of CD4+/CD8+ in serum were higher in group C at the same time (P<0.05).4. The expression of NF-κB were lower in hepatocyte in group A, but higher after CLP. To compared with group B, the expression of NF-κB were lower in group C at the same time (P<0.05) .5. According to Pearson correlation analysis, it is positive correlation between cyclooxygenase-2 mRNA and NF-κB, r=0.685, P=0.042.6. Hepatic pathologic injury were extenuated after injected with NS-398.7. Serum ALT, AST were obviously increased in group B than in group A, C (P<0.05). To compared with group B, it has statistical significance in group C after interfere with NS-398 at the same time.Conclusion1. NS-398, a selective cyclooxygenase-2 inhibitor, can obviously attenuate the expression of cox-2 mRNA.2. Cyclooxygenase-2 play an important role in sepsis, the pathway of cyclooxygenase-2 disordered organic immune state by changing the dynamic equilibrium between pro-inflammatory and anti-inflammatory cytokine and between CD4+ and CD8+ T cell. At the same time, it can affect to specificity and nonspecific immunity system and disorder immune state, damage to hepatic tissue at sepsis.3. NS-398 can inhibit the expression of NF-κB, revert the dynamic equilibrium between pro-inflammatory and anti-inflammatory cytokine and between CD4+ and CD8+ T cell, then correct immunological derangement condition of body and relieve hepatic injury and protect hepatocyte.
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