Lipidomics Study of Sepsis-Induced Liver and Lung Injury under Anti-HMGB1 Intervention

Sepsis
usually leads to lethal multiorgan dysfunction including
acute liver failure (ALF) and acute lung injury (ALI). This research
sought to reveal the lipid alteration of anti-high mobility group
box 1 (HMGB1) treatment in sepsis-induced ALF and ALI by lipidomics.
The cecal ligation and puncture-induced mouse model was established
and the anti-HMGB1 neutralizing antibody was administrated. The histopathological
characteristics and inflammatory factors were determined to assess
the efficacy of the antibody. Utraperformance liquid chromatography
coupled with quadrupole time-of-flight mass spectrometry was used
to determine lipid metabolism profiles in the liver and lung. The
underlying biomarkers were identified through multivariate statistical
analysis and correlation analysis with traditional physiological indicators.
The pathological and biochemical results demonstrated that anti-HMGB1
neutralizing antibodies mitigated ALF and ALI in mice. Three differential
metabolites in the liver and six various metabolites in the lung were
significantly reversed by anti-HMGB1 treatment, mainly involved in
arachidonic acid metabolism, glycerophospholipid metabolism, and sphingolipid
metabolism. Additionally, we investigated several traditional signaling
pathways associated with HMGB1. However, the correlation between these
traditional pathways and anti-HMGB1 intervention was not significant
in the current study. In conclusion, our finding provided some scientific
basis for targeting HMGB1 in sepsis-induced liver and lung injury.
Mass spectrometry data with identifier no. MTBLS6466 have been uploaded
to MetaboLights (http://www.ebi.ac.uk/metabolights/login).