Department of Pharmacy, Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China.
Department of Medical Comprehensive, Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China.
J Int Med Res. 2020 Oct;48(10):300060520961681. doi: 10.1177/0300060520961681.
This study evaluated the anti-fibrotic effects of oxymatrine and the role of endoplasmic reticulum (ER) stress in hepatic fibrosis (HF) in animal models.
The HF rat model was established by exposure to NaAsO, followed by treatment with oxymatrine. Biomarkers of HF and ER stress were measured. The difference in protein expression between groups was evaluated using isobaric tag for relative and absolute quantification (iTRAQ) analysis. The mechanism by which oxymatrine modulated ER stress to alleviate arsenic-induced HF was evaluated using LX2 hepatic stellate cells .
The rat model mimicked the pathological and physical phenotypes of HF including ER stress, oxidative stress, impaired liver function, and fibrosis. Treatment with oxymatrine suppressed these responses. Moreover, apoptosis, inflammation, and hepatic stellate cell activation were also inhibited by oxymatrine treatment. The differentially expressed proteins and pathways related to ER stress were identified in the HF and oxymatrine-treated groups iTRAQ analysis combined with liquid chromatography-mass spectrometry. LX2 cells were activated by NaAsO . Meanwhile, oxymatrine suppressed the activation of LX2 cells by alleviating ER stress and regulating cellular calcium homeostasis.
Oxymatrine could reverse NaAsO-induced HF by alleviating ER stress.
本研究评估了氧化苦参碱在动物模型中抗纤维化的作用及内质网（ER）应激在肝纤维化（HF）中的作用。
通过暴露于 NaAsO2 建立 HF 大鼠模型，然后用氧化苦参碱进行治疗。测量 HF 和 ER 应激的生物标志物。使用等重标记相对和绝对定量（iTRAQ）分析评估组间蛋白质表达的差异。使用 LX2 肝星状细胞评估氧化苦参碱调节 ER 应激缓解砷诱导的 HF 的机制。
大鼠模型模拟了 HF 的病理和生理表型，包括 ER 应激、氧化应激、肝功能受损和纤维化。氧化苦参碱治疗抑制了这些反应。此外，氧化苦参碱治疗还抑制了细胞凋亡、炎症和肝星状细胞活化。通过 iTRAQ 分析结合液相色谱-质谱鉴定了 HF 和氧化苦参碱治疗组中与 ER 应激相关的差异表达蛋白和途径。NaAsO2 激活了 LX2 细胞。同时，氧化苦参碱通过减轻 ER 应激和调节细胞内钙稳态来抑制 LX2 细胞的激活。
氧化苦参碱可通过减轻 ER 应激逆转 NaAsO2 诱导的 HF。
