中国病理生理杂志2026，Vol.42Issue(6)：1193-1198,6.DOI:10.3969/j.issn.1000-4718.2026.06.014
尾加压素Ⅱ通过抑制Nrf2信号通路激活铁死亡促进大鼠原代心脏成纤维细胞纤维化表型
Urotensin Ⅱ promotes fibrotic phenotype in primary rat cardiac fibro-blasts by activating ferroptosis via inhibition of Nrf2 signaling pathway
摘要
Abstract
AIM:To investigate whether urotensin II(UII)induces a fibrotic phenotype in rat cardiac fibro-blasts by triggering ferroptosis via the regulation of the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.METHODS:Primary cultured neonatal Wistar rat cardiac fibroblasts were randomly divided into four groups after 36 hours of incubation:the normal control group,the UII(100 nmol/L)group,the UII+Fer-1(10 μmol/L)group,and the UII+Nrf2 overexpression group.After 48 h of treatment,cell viability was evaluated using a CCK-8 assay.Intracellular reactive oxygen species(ROS)production was assessed by DCFH-DA fluorescence staining.The levels of ferrous iron(Fe²⁺),malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were measured using ELISA.The protein expression levels of Kelch-like ECH-associated protein 1(Keap1),Nrf2(total and nuclear protein),heme oxy-genase-1(HO-1),glutathione peroxidase 4(GPX4),ferritin,collagen I,and collagen III were quantified by Western blot.RESULTS:Compared with the control group,UII treatment significantly promoted fibroblast proliferation and ele-vated the intracellular levels of ROS,Fe²⁺,MDA,and ferritin(P<0.01).Furthermore,UII significantly upregulated the protein expression of Keap1,collagen I,and collagen III(P<0.01)and markedly downregulated the levels of GSH and SOD,as well as the expression of total/nuclear Nrf2,HO-1,and GPX4(P<0.01).Notably,these UII-induced oxidative and fibrotic alterations were effectively attenuated by the overexpression of either the ferroptosis inhibitor Fer-1 or Nrf2(P<0.01).CONCLUSION:UII promotes ferroptosis and a subsequent fibrotic phenotype in rat cardiac fibroblasts in vitro by suppressing the Nrf2 signaling pathway.Targeted inhibition of ferroptosis or intervention in the Nrf2 pathway may par-tially reverse these profibrotic effects in vitro.关键词
尾加压素Ⅱ/Nrf2信号通路/铁死亡/心脏成纤维细胞Key words
urotensin Ⅱ/Nrf2 signaling pathway/ferroptosis/cardiac fibroblasts分类
医药卫生引用本文复制引用
支杏敏,沃学文,刘浩,张梅菊,曹云龙,刘茜..尾加压素Ⅱ通过抑制Nrf2信号通路激活铁死亡促进大鼠原代心脏成纤维细胞纤维化表型[J].中国病理生理杂志,2026,42(6):1193-1198,6.基金项目
国家自然科学基金资助项目(No.82100244) （No.82100244）
中国博士后科学基金项目(No.2022M712012) （No.2022M712012）
山东省医药卫生科技发展计划项目(No.202003040648) （No.202003040648）
滨州医学院科研计划项目(No.BYFY2020KYQD40) （No.BYFY2020KYQD40）
