Lansoprazole promotes cisplatin-induced acute kidney injury by enhancing pyroptosis of renal tubular epithelial cells
10.19405/j.cnki.issn1000-1492.2024.11.004
- Author:
Xu Qi Xu Qi
1
;
Wu Yonggui Wu Yonggui
1
Author Information
1. Dept of Nephropathy , The First Afiliated Hospital of Anhui Medical University , Hefei 230022
- Publication Type:Journal Article
- Keywords:
acute kidney injury;
lansoprazole;
pyroptosis;
cisplatin;
inflammation
- From:
Acta Universitatis Medicinalis Anhui
2024;59(11):1911-1919
- CountryChina
- Language:Chinese
-
Abstract:
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 divided into normal control(NC) group,lansoprazole(LPZ) group,cisplatin(CIS) group and cisplatin+lansoprazole(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 electron microscopy was used to observe renal ultrastructure.Western blot and immunohistochemistry were used to detect 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-induced acute kidney injury by enhancing pyroptosis of renal tubular epithelial cells.
- Full text:2024122612462359836兰索拉唑通过增强肾小管上皮...亡促进顺铂诱导的急性肾损伤_徐起.pdf
