中国兽医杂志2025，Vol.61Issue(8)：37-45,9.DOI:10.20157/j.cnki.zgsyzz.2025.08.006
绿原酸调节Nrf2/GPX4信号通路干预脓毒症致急性肝损伤大鼠铁死亡的机制探究
Mechanistic Study on Chlorogenic Acid in Intervening Ferroptosis of Septic Acute Liver Injury Rats by Regulating Nrf2/GPX4 Signaling Pathway
摘要
Abstract
This study aimed to explore the effect of chlorogenic acid(CGA)on ferroptosis in rats with acute liver injury(ALI)induced by lipopolysaccharide(LPS),and its regulatory role on the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.Thirty-two male SD rats were randomly divided into four groups:control(CON),CON+CGA,LPS,and LPS+CGA.The CON group received no treatment;the LPS group received an intraperitoneal injection of LPS[10 mg/(kg·bw)];the CON+CGA and LPS+CGA groups were pretreated with CGA[20 mg/(kg·bw)]via intraperitoneal injection;one hour later,the LPS+CGA group received LPS[10 mg/(kg·bw)]injection.All rats were euthanized 4 hours after LPS administration,and blood and liver samples were collected.Serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured to assess liver function.Liver pathological changes were observed via hematoxylin-eosin(H.E.)staining.Oxidative stress indicators and ferrous iron(Fe2+)content were determined.Prussian blue staining was used to assess hepatic iron deposition.Real-time fluorescent quantitative PCR(qPCR)was conducted to analyze expression of ferroptosis-related genes,and Western blot was used to evaluate the expression of Nrf2 and ferroptosis-related proteins.Immunohistochemistry was employed to detect Nrf2 expression and nuclear translocation.The results showed that CGA significantly improved liver function(P<0.01),alleviated pathological liver damage,inhibited hepatic iron deposition,and reduced oxidative stress and Fe2+levels in the liver(P<0.01).Furthermore,CGA downregulated the mRNA levels of transferrin receptor 1(TFR1)and divalent metal ion transporter 1(DMT1)(P<0.01),while upregulating the mRNA expression of GPX4 and protein levels of Nrf2,solute carrier family 7 member 11(SLC7A11),and GPX4(P<0.01).These findings indicate that CGA exerts protective effects against LPS-induced ALI in rats by activating the Nrf2/GPX4 signaling pathway,thereby suppressing lipid peroxidation and ferroptosis in the liver.This study provides potential therapeutic targets and novel strategies for veterinary clinical management of sepsis-induced acute liver injury.关键词
绿原酸/急性肝损伤/脂质过氧化/铁死亡/Nrf2/GPX4通路Key words
chlorogenic acid/acute liver injury/lipid peroxidation/ferroptosis/Nrf2/GPX4 pathway分类
农业科技引用本文复制引用
黄静,王铭铭,刘敬轩,淳海清,刘恩喜,唐琦超..绿原酸调节Nrf2/GPX4信号通路干预脓毒症致急性肝损伤大鼠铁死亡的机制探究[J].中国兽医杂志,2025,61(8):37-45,9.基金项目
吉林农业科技学院国家级大学生科技创新创业训练计划项目(GJ202211439006) （GJ202211439006）
深圳市瑞鹏公益基金会与新瑞鹏宠物医疗集团有限公司共同资助高校青年教师科研基金项目(RPJJ2021027) （RPJJ2021027）
