Andrographolide regulates SLC7A11/GPX4 axis in ferroptosis to attenuate intestinal injury in sepsis
10.19405/j.cnki.issn1000-1492.2023.12.016
- VernacularTitle:穿心莲内酯调控铁死亡中SLC7A11/GPX4轴减轻脓毒症肠损伤
- Author:
Ming HUANG
1
;
Yixin ZHANG
;
Guodong CAO
;
Youcheng ZENG
;
Liang LIN
;
Xiaoyue WANG
;
Qinghong CHENG
Author Information
1. 石河子大学医学院,石河子 832000
- Keywords:
sepsis;
intestinal injury;
andrographolide;
ferroptosis;
SLC7A11/GPX4 pathway;
I-FABP
- From:
Acta Universitatis Medicinalis Anhui
2023;58(12):2094-2100
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.
