中国临床医学2025，Vol.32Issue(4)：593-603,11.DOI:10.12025/j.issn.1008-6358.2025.20250453
槲皮素通过Nrf2/HO-1通路改善血管紧张素Ⅱ诱导的血管平滑肌细胞表型转化
Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway
摘要
Abstract
Objective To investigate the protective effect and mechanism of quercetin(QR)against angiotensinⅡ(AngⅡ)-induced injury and phenotypic transformation in vascular smooth muscle cells(VSMCs).Methods VSMCs were treated with AngⅡand divided into four groups:control(Ctrl),QR control,model(AngⅡ),and treatment(AngⅡ+QR)groups.Intracellular reactive oxygen species(ROS)level and superoxide dismutase(SOD)activity were measured.Western blotting was used to assess protein expression related to inflammation,apoptosis,extracellular matrix(ECM)remodeling,phenotypic transformation,and the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to quantify mRNA levels of inflammatory cytokines(interleukin[IL]-1β,IL-6,and tumor necrosis factor-α[TNF-α]).Cell migration was evaluated using a scratch assay.A rescue experiment employing the Nrf2 transcriptional activity inhibitor ML385 was conducted to further validate protective mechanism of QR for VSMCs.Results Compared to the Ctrl group,AngⅡ-treated VSMCs exhibited significantly higher ROS levels,suppressed SOD activity,upregulated expression of inflammatory proteins and mRNA(IL-1β,IL-6,TNF-α),increased matrix metalloproteinase(MMP)protein expression(P＜0.05),enhanced migration capacity,reduced expression of contractile phenotype markers(smooth muscle 22 alpha[SM22α]and α-smooth muscle actin[α-SMA]),upregulated expression of the synthetic phenotype marker osteopontin(OPN),and significantly increased apoptosis(P＜0.05).QR intervention significantly reduced intracellular ROS level,increased SOD activity,decreased protein expression of vascular cell adhesion molecule-1(VCAM-1)and phosphorylated nuclear factor-κB(NF-κB),downregulated inflammatory cytokine transcription,upregulated contractile phenotype marker expression,and attenuated apoptosis and migration capacity(P＜0.05).The rescue experiment confirmed that QR alleviated AngⅡ-induced oxidative stress,inflammation-related injury,and suppressed the transition of VSMCs towards a synthetic phenotype via activation of Nrf2.Conclusions QR mitigates AngⅡ-induced oxidative stress,inflammation,and apoptosis in VSMCs,inhibits ECM remodeling and VSMCs migration,and consequently suppresses VSMCs phenotypic transformation,primarily through promoting Nrf2 expression.关键词
槲皮素/颅内动脉瘤/血管平滑肌细胞/氧化应激/表型转化/核因子E2衍生相关因子2Key words
quercetin/intracranial aneurysm/vascular smooth muscle cell/oxidative stress/phenotypic transformation/nuclearfactor erythroid 2-related factor 2分类
医药卫生引用本文复制引用
阿捕都热西提•麦麦提依明,朱巍..槲皮素通过Nrf2/HO-1通路改善血管紧张素Ⅱ诱导的血管平滑肌细胞表型转化[J].中国临床医学,2025,32(4):593-603,11.基金项目
国家自然科学基金(82171311,82330039).Supported by National Natural Science Foundation of China(82171311,82330039). （82171311,82330039）
