Lansoprazole promotes cisplatin-induced acute kidney injury by enhancing pyroptosis of renal tubular epithelial cells
Objective To investigate the effect of lansoprazole(LPZ)on cisplatin-induced acute kidney injury in mice and renal tubular epithelial cell injury.Methods C57BL/6J mice and renal tubular epithelial cells were di-vided into normal control(NC)group,lansoprazole(LPZ)group,cisplatin(CIS)group and cisplatin+lanso-prazole(CIS+LPZ)group.In animal experiments,LPZ(25 mg/kg)was dissolved in normal saline,and the mice were intraperitoneally injected with LPZ for three consecutive days followed by cisplatin(20 mg/kg).Mice were fed normally for 3 days,and serum samples were collected to detect serum creatinine(CRE)and blood urea nitrogen(BUN)levels.HE staining and PAS staining were used to observe renal pathology,and transmission elec-tron microscopy was used to observe renal ultrastructure.Western blot and immunohistochemistry were used to de-tect the changes in the expression levels of KIM-1,NGAL and pyroptosis-related proteins.In the cell experiment,the cells were treated with cisplatin(20 μmol/L)and LPZ(5 μmol/L)for 24 hours,and the expressions of KIM-1,NGAL and pyroptosis-related factors were detected by Western blot and Real-time PCR.Results Compared with the NC group,CRE and BUN levels increased in the CIS group,and LPZ treatment aggravated the serological indicators of the mice(P＜0.001).Histopathological examination showed that compared with the CIS group,the LPZ+CIS group had obvious renal tubular dilatation,inflammatory cell infiltration and glycogen deposition in the renal tissue(P＜0.001).Electron microscopy showed swelling of mitochondria,increased membrane density and decreased or absent mitochondrial crista in CIS group,which were aggravated by LPZ+CIS group.In vivo and in vitro experiments confirmed that LPZ treatment promoted CIS-induced acute kidney injury in mice and increased the expression levels of kidney injury factors KIM-1,NGAL and key factors of renal pyroptosis(Caspase 1,GSDMD,NLRP3 and IL-18)in renal tubular epithelial cells(P＜0.001).Conclusion Lansoprazole promotes cisplatin-in-duced acute kidney injury by enhancing pyroptosis of renal tubular epithelial cells
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