同济大学学报（医学版）2025，Vol.46Issue(6)：828-839,12.DOI:10.12289/j.issn.2097-4345.25115
红景天苷上调EFNA1激活PI3K/AKT/Nrf2信号通路减轻顺铂引起的急性肾损伤
Salidroside attenuates cisplatin-induced acute kidney injury by activating PI3K/AKT/Nrf2 signaling pathway via upregulating EFNA1
摘要
Abstract
Objective To investigate the protective mechanism of salidroside(SAL)in cisplatin nephrotoxicity.Methods The protective effect of SAL against cisplatin-induced acute kidney injury was determined by in vitro and in vivo model,and the expression of renal injury markers and apoptosis-related proteins were detected by Western blotting assay and serum examination.Flow cytometry was used to detect apoptosis and reactive oxygen species(ROS),and transmission electron microscopy was used to observe mitochondrial damage.Transcriptome sequencing was used to analyze differentially expressed genes,and relevant pathways were screened by combining GO/KEGG enrichment;the siRNA was used to knock down the target gene to verify the protective role of SAL by upregulating EFNA1.In addition,the phosphorylation levels of phosphoinositide 3-kinase(PI3K)and protein kinase B(AKT)and the nuclear localization of Nrf2 were detected,and changes in the activities of antioxidant enzymes[superoxide dismutase(SOD),glutathione peroxidase(GSH-px),catalase(CAT)]were assessed.Results SAL reduced the levels of renal injury markers,promoted the levels of antioxidant enzymes and inhibited ROS,reduced mitochondrial damage and apoptosis in cisplatin-treated HK2 cells and mice.Transcriptome sequencing combined with WB results showed that SAL promoted the phosphorylation of PI3K and AKT through up-regulation of EFNA1,mediated the nuclear translocation of the downstream protein Nrf2,and ultimately elevated the levels of antioxidant enzymes,such as SOD,CAT,and GSH-px,and inhibited apoptosis to alleviate cisplatin-induced acute kidney injury.Conclusion SAL inhibits oxidative stress and attenuates cisplatin-induced acute kidney injury by up-regulating EFNA1 to activate the PI3K/AKT/Nrf2 pathway.关键词
红景天苷/顺铂/急性肾损伤/EFNA1/活性氧Key words
salidroside/cisplatin/acute kidney injury/EFNA1/reactive oxygen species分类
医药卫生引用本文复制引用
艾力亚尔·艾尼瓦尔,孙淑雯,阿依努尔·伯合提亚尔,张竞成,蒋宇峰,鄢阳..红景天苷上调EFNA1激活PI3K/AKT/Nrf2信号通路减轻顺铂引起的急性肾损伤[J].同济大学学报（医学版）,2025,46(6):828-839,12.基金项目
上海市崇明区"可持续发展科技创新行动计划"(CKY2023-47) （CKY2023-47）
