Paeoniflorin alleviates sepsis-associated acute kidney injury through JNK/NEK7/NLRP3 pathway
10.3969/j.issn.1000-4718.2024.09.017
- VernacularTitle:芍药苷通过JNK/NEK7/NLRP3通路缓解脓毒症相关急性肾损伤
- Author:
Ming ZHANG
1
;
Jiao LEI
;
Yu GONG
;
Jing XIE
;
Ruonan LI
;
Yuqing MA
Author Information
1. 兰州大学第一临床医学院,甘肃 兰州 730000
- Keywords:
sepsis;
acute kidney injury;
paeoniflorin;
cellular pyroptosis;
NEK7;
NLRP3
- From:
Chinese Journal of Pathophysiology
2024;40(9):1711-1717
- CountryChina
- Language:Chinese
-
Abstract:
AIM:The effects and mechanisms of paeoniflorin(PF)on sepsis-associated acute kidney injury(SA-AKI)in mice were investigated based on cellular pyroptosis and the JNK/NEK7/NLRP3 pathway.METHODS:A murine SA-AKI model was established by intraperitoneal injection of lipopolysaccharide(LPS).Twenty-four male C57BL/6J mice aged 6～8 weeks were divided into four groups(n=6)using a randomized numerical table method:control(Con)group(an equal amount of DMSO-containing PBS was injected intraperitoneally at the same time);LPS group(LPS was injected intraperitoneally at 15 mg/kg);LPS+PF group(PF was injected intraperitoneally at 50 mg/kg for 30 min prior to modeling);and LPS+PF+anisomycin group(intraperitoneal injection of PF 50 mg/kg and JNK agonist anisomycin 20 mg/kg 30 min before modeling).Samples were taken 24 h after modeling.HE staining was used to observe the pathological changes in renal tissues,and Paller scoring of renal injury was performed.ELISA was used to detect the levels of renal in-jury markers:blood creatinine(Scr),kidney injury molecule 1(KIM-1),and the inflammatory factors interleukin 1β(IL-1β)and IL-18.Western blot was used to detect changes in phosphorylated c-Jun N-terminal kinase(p-JNK),NIMA-relat-ed expressed kinase 7(NEK7),nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3),and N-ter-minal fragment of gasdermin D(GSDMD-N)protein levels.RESULTS:Compared with the Con group,HE staining in the LPS group showed congestion and edema in renal tissues,granular or cell-like tubular patterns in the dilated tubular lu-men of renal tubules,and congestion and edema in the renal interstitium.Paller scores,Scr,serum KIM-1,IL-1β,and IL-18 levels in renal tissues were elevated(P<0.05).The expression of p-JNK,NEK7,NLRP3,and GSDMD-N also in-creased(P<0.05).Compared with the LPS group,the LPS+PF group exhibited reduced renal histopathological injury,decreased Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and decreased protein expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).Compared with the LPS+PF group,the LPS+PF+anisomycin group showed increased renal histopathological injury,Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and increased expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).CONCLUSION:Paeoniflorin may at-tenuate SA-AKI by inhibiting the JNK/NEK7/NLRP3 signaling pathway and downregulating cellular pyroptosis.
