中国实验动物学报2025，Vol.33Issue(2)：157-168,12.DOI:10.3969/j.issn.1005-4847.2025.02.001
常春藤素皂苷元介导Axin2/AREG轴抑制炎症缓解小鼠急性肾损伤
Hederagenin mediates Axin2/AREG axis to inhibit inflammation and alleviate acute kidney injury in mice
摘要
Abstract
Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.关键词
常春藤素皂苷元/急性肾损伤/Axin2/AREG/炎症Key words
hederagenin/acute kidney injury/Axin2/AREG/inflammation分类
生物学引用本文复制引用
徐玲慧,梁颖兰,粟宏伟,李健春,李贵平,王丽,邹远霞..常春藤素皂苷元介导Axin2/AREG轴抑制炎症缓解小鼠急性肾损伤[J].中国实验动物学报,2025,33(2):157-168,12.基金项目
国家自然科学基金(82104665),四川省科技计划资助(2022YFS0621),西南医科大学科技项目资助(2023ZYYQ01).Funded by National Natural Science Foundation of China(82104665),Sichuan Science and Technology Program(2022YFS0621),Southwest Medical University Technology Program(2023ZYYQ01). （82104665）
