Resolvin D1 prompts inflammation resolution in ACLF rats by increasing
the proportion of Treg
Abstract
Objective: Acute-on-chronic liver failure (ACLF) causes organ system
failures and the high mortality, and there is currently a lack of
effective means of prevention. The purpose of the study was to explore
the therapeutic effects of Resolvin D1 (RvD1) on ACLF rats and its
underlying mechanism. Methods: ACLF rat model was constructed by
intraperitoneally injecting CCl4 and porcine serum for 6 weeks and then
induced acute liver injury by treating with both LPS and D-Galn. The
ACLF rats were pretreated with different doses of RvD1 (0.3 or 1 ug/kg)
before the acute liver injury. Biochemical analysis, H&E and sirius red
staining, flow cytometry assay and real-time PCR were used to assess rat
liver histopathological injury, determine the Treg cell frequencies in
spleen and the mRNA levels of transcription factors and immunologic
cytokines in liver. Results: The necro-inflammatory scores and the serum
levels of transaminase significantly increased in ACLF model rats
compared to those in normal control rats, with the peak at 8 h. Low-dose
of RvD1 could limit necrosis and inflammation and decrease the ALT level
of ACLF rats. The degree of damage in ACLF rats was related to the
increased mRNA levels of IL-17 and IL-6 in the ACLF rats’ liver and Treg
cells reduction in the spleen. Low-dose of RvD1 could protect against
liver injury in ACLF rats, as indicated by increasing Treg cell
frequency in rats’ spleen and the mRNA levels of Foxp3/RORγ and
decreasing the expression of both IL-6 and IL-17. Conclusion: Low-dose
of RvD1 plays a protective role in ACLF rats by increasing the
proportion of Treg cells. It is the first time to reveal the function of
RvD1 in the treatment of ACLF. This work may help us clarify the
pathogenesis of ACLF and find effective therapeutic drugs for ACLF.