Mechanism of andrographolide alleviates lipopolysaccharide-induced fer-roptosis in renal tubular epithelial cells
10.12138/j.issn.1671-9638.20244536
- VernacularTitle:穿心莲内酯减轻脂多糖诱导的肾小管上皮细胞铁死亡机制
- Author:
Yi-Xin ZHANG
1
;
Ming HUANG
;
Guo-Dong CAO
;
You-Cheng ZENG
;
Liang LIN
;
Xiao-Yue WANG
;
Qing-Hong CHENG
Author Information
1. 石河子大学第一附属医院重症医学二科,新疆石河子 832000
- Keywords:
andrographolide;
renal tubular epithelial cell;
HK-2;
ferroptosis;
SLC7A11;
Xc system;
mechanism
- From:
Chinese Journal of Infection Control
2024;23(5):568-573
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of andrographolide(AG)on lipopolysaccharide(LPS)-induced ferroptosis in renal tubular epithelial cells(HK-2 cells).Methods HK-2 cells were treated with LPS to simulate the in vitro HK-2 injury model of sepsis.The cells were further treated with AG of 5,10,20,40 μmol/L and randomly divided into control group,LPS group,LPS+dimethyl sulfoxide group(DMSO group),and AG group.Cell viability was detected by the CCK-8 method,and the optimal concentrations of LPS and AG were screened.Cell morphological change,the levels of kidney injury markers,including neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS),as well as the expression levels of ferroptosis regulatory proteins such as solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and ferritin in each group were compared,and the pro-tective effect of AG treatment on the cells was evaluated.Results Compared with the control group,the cell viabi-lity and GSH content decreased significantly in HK-2 cells treated with 10 μg/mL LPS;cell shrinkage and adhesion ability were poor;the contents of oxidative products MDA and ROS,as well as the levels of kidney injury markers NGAL and KIM-1 increased significantly,while expression levels of SLC7A11 and GPX4 protein decreased;ferritin expression level increased;differences were all statistically significant(all P＜0.05).Compared with LPS group,the cell viability,GSH content,as well as protein expression levels of SLC7A11 and GPX4 increased significantly after AG intervention,while ferritin expression level decreased,differences were all significant(all P＜0.05).MDA content,ROS fluorescence intensity,and the levels of kidney injury markers NGAL and KIM-1 decreased sig-nificantly,difference were all significant(all P＜0.05).Conclusion AG has a protective effect on LPS-induced HK-2 cell injury,possibly by activating SLC7A11/GPX4 pathway,reducing oxidative stress,up-regulating antioxi-dant enzyme activity,and alleviating ferroptosis.
