Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia

Figure 5

The inhibition of XO reduced inflammation and apoptosis in SI-AKI mice. (a–c) The levels of TNF-α, IL-1β, and IL-6 in renal homogenates of SI-AKI mice were detected by ELISA. (d, g) Immunofluorescence detection of neutrophils in the kidneys of SI-AKI mice by anti-MPO antibody (400x magnification). (e, h) Immunofluorescence detection of macrophages in the kidneys of SI-AKI mice by anti-F4/80 antibody (400x magnification). (f, i) Representative TUNEL-stained sections of the kidney in SI-AKI mice (400x magnification). Semiquantitative analysis of TUNEL-positive cells in each group is also displayed. (j–l) After the downregulation of XO, mice were treated with LPS (10 mg/kg), and the levels of TNF-α, IL-1β, and IL-6 in renal homogenates of SI-AKI mice were detected by ELISA. (m and p, n and q) After knockdown of XO with pAAV-shRNA, immunofluorescence detection of neutrophils and macrophages in the kidneys of SI-AKI mice by anti-MPO and anti-F4/80 antibodies (400x magnification). (o, r) Kidney cell apoptosis was analyzed with TUNEL staining in SI-AKI mice after XO knockdown.  μm. , , and vs. control; ^#, ^##, and ^### vs. LPS+Veh or LPS+Ctr-shR (). Ctrl: control; Veh; vehicle; LPS: lipopolysaccharide; Feb: febuxostat; TNF: tumor necrosis factor; IL: interleukin; MPO: myeloperoxidase; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling.