Abstract：Objective To study the protective effect and possible mechanism of glycyrrhizic acid (GA) on sepsis induced acute kidney injury in rats. Methods SD rats were divided into sham operation group, GA 50 mg/kg group, sepsis group, sepsis +GA 25 mg/kg group, and sepsis +GA 50 mg/kg group, with six rats in each group. Sepsis group rats were intraperitoneally injected with lipopolysaccharide (LPS) at 5 mg/kg. HBZY-1 cells were divided into control group, 100 μmol/L GA group, LPS group, LPS+GA 50 μmol/L group and LPS+GA 100 μmol/L group. LPS group was cultured with 10 μg/ml LPS for 24 h to establish nephritis model. Histopathological changes of kidney were observed by HE staining; the contents of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in renal tissue were determined by enzyme-linked immunosorbent assay; HBZY-1 cells apoptosis, inflammation and oxidative stress related protein expression were analyzed by Western blot. Results The renal interstitium, glomerulus and tubules of sepsis rats were infiltrated with inflammatory cells, and some renal tubules were swollen and vacuolar degeneration. The above pathological changes in the renal tissues of sepsis rats were significantly relieved after GA treatment. The expression levels of TNF-α, ICAM-1 and VCAM-1 in rat renal tissues of sepsis+GA 25 mg/kg group and sepsis+GA 50 mg/kg group were lower than those of sepsis group (P < 0.05). The level of MCP-1 in rat renal tissue of sepsis+GA 50 mg/kg group was lower than that of sepsis group (P < 0.05). The expression levels of cyclooxygenase-2 and nuclear factor-κB protein in HBZY-1 cells in LPS+50 μmol/L and LPS+100 μmol/L GA groups were lower than those in LPS group (P < 0.05 or P < 0.01), the inducible nitric oxide synthase level in LPS+GA 100 μmol/L group was lower than that in LPS group (P < 0.01). The relative expression of Bcl-2/Bax in HBZY-1 cells in LPS+GA 100 μmol/L group was higher than that in LPS group (P < 0.01). The expression of cleaved Caspase-3 protein in HBZY-1 cells in LPS+GA 50 μmol/L and LPS+GA 100 μmol/L groups were lower than those in LPS group (P < 0.01). The heme oxygenase-1 protein expression level in LPS+GA 50 μmol/L group and LPS+GA 100 μmol/L group were higher than those in LPS group (P < 0.01). The expression level of p-ERK protein in LPS+GA 100 μmol/L group was higher than that in LPS group (P < 0.01). Conclusion GA has a protective effect on acute kidney injury induced by sepsis in rats, and its mechanism may be related to inhibiting apoptosis, oxidative stress and inflammatory response.
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