Xuebijing injection alleviates cytokine-induced inflammatory liver injury in CLP-induced septic rats through induction of suppressor of cytokine signaling 1

Abstract

Dysregulation of inflammatory cytokines and liver injury are associated with the pathogenesis of sepsis. Xuebijing injection, a Chinese herbal medicine, has been used in the treatment of sepsis and can contribute to the improvement of patients' health. However, the underlying molecular mechanisms are not yet clearly illuminated. In the present study, a septic rat model with liver injury was established by the cecal ligation and puncture (CLP) method. Histological alterations to the liver, activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), levels of inflammatory cytokine secretion and the expression of suppressors of cytokine signaling 1 (SOCS-1) in the CLP model rats with and without Xuebijing treatment were determined. The results showed that Xuebijing injection ameliorated the pathological changes in liver tissues caused by sepsis, and reduced the sepsis-induced elevation in serum ALT and AST levels. Furthermore, Xuebijing injection markedly downregulated the expression of tumor necrosis factor α and interleukin (IL)-6, and upregulated the expression of IL-10. More importantly, SOCS1 expression levels at the protein and mRNA levels were further increased by Xuebijing. These findings demonstrate that Xuebijing injection can significantly alleviate liver injury in CLP-induced septic rats via the regulation of inflammatory cytokine secretion and the promotion of SOCS1 expression. The protective effects of Xuebijing injection suggest its therapeutic potential in the treatment of CLP-induced liver injury.

Keywords: SOCS-1; Xuebijing injection; sepsis.

Figure 1.

Effects of Xuebijing injection on CLP-induced histological liver injury in CLP-induced septic rats. Con group, control group; CLP group, cecal ligation and puncture group; XT group, CLP surgery plus Xuebijing injection treatment. Liver sections with hematoxylin and eosin staining (magnification, ×200).

Figure 2.

Effects of Xuebijing injection on the levels of (A) ALT and (B) AST in CLP-induced septic rats. ALT, alanine aminotransferase; AST, aspartate aminotransferase; Con group, control group; CLP group, cecal ligation and puncture group; XT group, CLP surgery plus Xuebijing injection treatment. Data are expressed as the mean ± standard deviation (n=6). *P<0.05 vs. the Con group; ^#P<0.05 vs. the CLP group.

Figure 3.

Effects of Xuebijing injection on the secretion of inflammatory cytokines in CLP-induced septic rats. Expression levels of (A) TNF-α, (B) IL-6 and (C) IL-10 were determined. TNF, tumor necrosis factor; IL, interleukin; Con group, control group; CLP group, cecal ligation and puncture group; XT group, CLP surgery plus Xuebijing injection treatment. Values are expressed as the mean ± standard deviation (n=6). *P<0.05 vs. the Con group; ^#P<0.05 vs. the CLP group.

Figure 4.

Effects of Xuebijing injection on the expression of SOCS-1 in CLP-induced septic rats. (A) SOCS-1 mRNA expression levels determined by reverse transcription-quantitative polymerase chain reaction. Values are expressed as the mean ± standard deviation of 6 rats in each group. *P<0.05 vs. the Con group; ^#P<0.05 vs. the CLP group. (B) A representative Western blot from three experiments is shown; β-actin was used as a loading control. SOCS, suppressors of cytokine signaling; Con group, control group; CLP group, cecal ligation and puncture surgery group; XT group, CLP surgery plus Xuebijing injection treatment.