The time related concentration of serum HMGB1 and TLR4 in CLP rat model

Objective To explore the mechanism of inflammatory response in sepsis and look for potential biomarkers for early diagnosis and treatment of sepsis, we examine the time related concentration of serum HMGB1 and TLR4 in CLP rat model. Methods A septic rat model was built with cecal ligation and puncture. The rats were randomized into three groups: CLP group, CLP with HMGB1 inhibitor group (HMGB1 group) and CLP with TLR4 inhibitor group (TLR4 group), control group and sham operation group (sham group). At 2, 4, 8, 12, 24, 48 h after operation/sham operation, serum HMGB1 and TLR4 concentration were examined with ELISA. Results Serum HMGB1 increased significantly than that in sham group and control group, peaking at 24 h (P<0.05); compared with CLP group, in HMGB1 group, HMGB1 inhibitor started to inhibit HMGB1 at 4 hours after operation significantly (P<0.05); compared with CLP group, in TLR4 group, TLR4 inhibitor decreased serum HMGB1 concentration significantly from 2 to 24 hours after operation (P<0.05); compared with HMGB1 inhibitor, TLR4 inhibitor worked earlier (at 2h after operation, P<0.05) and stronger (at 12 h and 24 h after operation, P<0.05). Serum TLR4 concentration showed a biphasic expression in CLP group (at 8 h and 24 h after operation, P<0.05); compared with CLP group, serum TLR4 concentration became monophasic with peaking at 8 h after operation when treated with HMGB1 (P<0.05); however, with TLR4 inhibitor treatment, the expression of serum TLR4 still appeared a biphasic expression, but peaking earlier and had a higher peak (peaking at 4 h and 12 h after operation, P<0.05). Conclusion HMGB1 can play a role in the inflammatory response of sepsis through TLR4 signal pathway. Inflammatory response of sepsis is a complex, ″cross-link″ system, which means only changing/influencing certain ″key-signal transcriptional regulation factor″ would be with limited effect. Key words: Sepsis; HMGB1; TLR4