Thymoquinone modulates the expression of sepsis-related microRNAs in a CLP model.

Abstract

Sepsis is a clinical syndrome common in critical care settings. In the present study, the therapeutic effect of thymoquinone (TQ) on the expression of sepsis-related microRNAs (miRNAs/miRs), levels of inflammatory markers, organ dysfunction and mortality were investigated in a cecal ligation and puncture (CLP) rat model. A single dose of TQ (1 mg/kg) was administered to animals 24 h after CLP and the mortality rate was assessed up to 7 days following the induction of sepsis. In addition, blood samples were collected at different time points and the expression levels of miRNAs (i.e. miR-16, miR-21, miR-27a and miR-34a) were examined, along with the levels of inflammatory cytokines (i.e. TNF-α, IL-1α, IL-2, IL-6 and IL-10) and sepsis markers (i.e. C-reactive protein, endothelial cell-specific molecule-1, VEGF, procalcitonin and D-dimer). Liver, kidney and lung tissues were also collected for further histological examination. Treatment with TQ significantly downregulated the miRNA expression levels, as well as the levels of inflammatory cytokines and early-stage sepsis biomarkers by 30-70% at 12-36 h (P<0.05). Furthermore, CLP model rats treated with TQ exhibited an ~80% increase in survival rate compared with that in the untreated CLP group. In addition, TQ induced the preservation of organ function and structure. In conclusion, the present study demonstrated a promising therapeutic effect of TQ against the sequelae of sepsis.