【Objective】 To investigate the molecular mechanisms about ethyl pyruvate (EP) inhibit the expression and releasing of HMGB1 by macrophages in sepsis. 【Methods】 The murine macrophage-like cell line RAW264.7 cultured in vitro divided into LPS group and LPS +EP group. These groups were stimulated with 100 ng/mL LPS and 100 ng/mL LPS mixed with 5 mmol/L EP respectively. Western blot was used to detect the expression of protein in the cells about p-p38MAPK

CBP

NF-κB in nucleus and NF-κB in cytoplasm at different time-points. Immunocytochemistry and confocal laser scanning microscopy were used to confirm the change of p38-MAPK

NF-κB

and CBP in cultured cells. The expression of HMGB1 mRNA in cultured cells was determined by Real-time PCR. The content of HMGB1 protein in cultured cells supernatant were detected by ELISA. 【Results】 After stimulated by LPS and LPS+EP respectively from 2 to 6 hour

the protein level of p-p38MAPK in cells while this increase group of LPS+EP was obviously slower than the group of LPS. The expression of NF-κB protein in cytoplasm reduce while the same factor in nuclear increase gradually and this phenomenon was more weaker in LPS+EP group than that in LPS group. The protein of CBP in cells gradually increase while the protein of CBP in LPS+EP group was lower than that in LPS group. With variation of p38-MAPK

NF-κB

and CBP

the expression of HMGB1 mRNA in the cells of LPS group was decreased significantly than the ones in LPS group after each group stimulated with LPS and LPS+EP 24 h

36 h

and 48 h

respectively. The content of HMGB1 protein in cultured cells supernatant of LPS+EP group was obviously lower than that of LPS group at the same time points after separately stimulated by LPS+EP and LPS from 18 h to 48 h. 【Conclusion】 EP inhibits the expression of signal molecules in monocyte-macrophages including p38-MAPK

NF-κB

and CBP so as to inhibit the expression and releasing of HMGB1 by macrophages which induced by LPS in sepsis.