Scoparone alleviates sepsis-related acute kidney injury mediated by jumonji domain-containing protein 3 and myeloid differ-entiation protein-2
Objective To investigate the mechanism of scoparone(Sco)alleviating sepsis-related acute kidney injury(AKI).Methods Twenty-four C57BL6 mice were randomly divided into control group,LPS group,low-Sco group and high-Sco group with 6 mice in each group.The sepsis-related AKI was induced by intraperitoneal injection of LPS 10 mg/kg in mice of last 3 groups.Mice in low-and high-Sco groups were intraperitoneally injected 40 mg/kg and 80 mg/kg Sco group after successful modeling,respectively;while mice in the control group were intraperitoneally injected with 0.9%sodium chloride solution(2 mL/kg).HE staining and TUNEL staining were used to detect the degree of renal tissue injury and apoptosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)levels were detected by ELISA.The expression levels of JMJD3 and MD-2 protein in renal tissue were detected by Western blot.Human renal tubular epithelial cells HK-2 were treated with LPS(1 μg/mL)for 24 h to establish a sepsis cell model.They were randomly divided into control group,LPS group,LPS+30 μmol/L Sco group,LPS+60 μmol/L Sco group,LPS+60 μmol/L Sco+overexpression control group and LPS+60 μmol/L Sco+JMJD3 overexpression group.Apoptosis was detected by flow cytometry,and the expression levels of JMJD3 and MD-2 protein were detected by Western blot.Results Compared with the control group,the renal tissue of mice in LPS group showed obvious pathological changes,including partial renal tubule deformation,edema of renal tubule epithelial cells,infiltration of perirenal interstitial inflammatory cells,enhanced apoptosis signal(brown),increased expression of JMJD3 and MD-2 protein,and increased serum Scr and BUN levels.Compared with LPS group,the above pathological changes in kidney tissues of mice in LPS+40 mg/kg Sco group and LPS+80 mg/kg Sco group were significantly improved,the expression levels of JMJD3 and MD-2 protein were decreased,and the serum levels of Scr and BUN were also decreased.The change of LPS+80 mg/kg Sco group was more obvious.Compared with the control group,the apoptosis level and the expression level of JMJD3 and MD-2 protein were increased in LPS group.Compared with LPS group,the above change trend was reversed after Sco treatment,and the higher the Sco concentration was,the more significant the change was.In addition,after overexpression of JMJD3,the apoptosis level and the expression levels of JMJD3 and MD-2 protein were significantly increased.Conclusion Sco can alleviate the sepsis-related AKI by inhibiting the expression of JMJD3 and MD-2 in renal tubular epithelial cells,and reducing cell apoptosis.
SepsisAcute kidney injuryScoparoneJumonji domain-containing protein 3Myeloid differentiation protein-2