Protective effect and mechanism of ulinastatin on sepsis-acute kidney injury by regulating NF-κB signaling pathway
10.3760/cma.j.issn.1671-0282.2023.12.018
- VernacularTitle:乌司他丁调控NF-κB信号通路对脓毒症急性肾损伤作用机制研究
- Author:
Chunmin ZHANG
1
;
Wenmin YANG
;
Yongmin LIN
;
Peidan HU
;
Meiling SU
;
Yiyu YANG
;
Yan Fei CHEN
Author Information
1. 广州市妇女儿童医疗中心儿童重症监护室，广州 510120
- Keywords:
Ulinastatin;
Sepsis;
Acute kidney injury;
Mitochondrial;
NF-κB
- From:
Chinese Journal of Emergency Medicine
2023;32(12):1680-1685
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of ulinastatin on sepsis-acute kidney injury (SA-AKI) by NF-κB signaling pathway.Methods:Total of 60 mice were randomly(random number) divided into sham group, cecal ligation puncture group (CLP group) and ulinastatin treatment group (CLP+UTI group). Ulinastatin treatment group was intraperitoneally injected with ulinastatin 50 000 U/kg once a day. 24 hours after operation, five mice were sacrificed, the kidney tissues were collected to observe renal histopathology by HE staining. The macrophage infiltration was observed by immunohistochemistry. The remaining mice in each group were used to calculate the survival rate of 7-day after operation. HK-2 cells were stimulated by LPS to obtain the SA-AKI model, and the cells were divided into control group, LPS group and LPS + UTI group. CCK-8 assay was used to detect cell viability, EdU assay was used to detect cell proliferation, and JC-1 assay was used to detect mitochondrial damage. The phosphorylation degree of NF-κB was detected by western blot. Inflammatory factors concentrations of cellular supernatant were detected by ELISA assay.Results:Compared with the sham group, the kidney tissue of mice in CLP group showed that kidney pathological obvious changed, the infiltration of macrophages increased, and the survival rate of mice decreased. CLP+ UTI group reduced the pathological changes and the infiltration of macrophages, improved the survival rate of mice. Compared with control group, LPS group obviously inhibited the cells activity and proliferation of HK-2 cells, damaged the mitochondrial membrane potential of HK-2 cells. Compared with LPS group, LPS+ UTI group attenuated the phosphorylation of NF-κB, decreased the secretion of inflammatory factors, rescued the activity and proliferation of HK-2 cells, and reduced the damage of HK-2 mitochondrial membrane potential.Conclusions:Ulinastatin can reduce mitochondrial damage, inhibit the secretion of inflammatory factors and improve the function of renal tubular epithelial cells through regulating NF-κB signaling pathway.
