黄芩苷通过调控铁死亡减轻H9c2细胞缺氧复氧损伤及其机制研究*
作者：李家权1，许 锦2，谭子富1，方孝俊1
单位：1.恩施土家族苗族自治州中心医院，湖北 恩施 445000； 2.恩施市中心医院，湖北 恩施 445000
引用：引用：李家权，许锦，谭子富，方孝俊.黄芩苷通过调控铁死亡减轻H9c2细胞缺氧复氧损伤及其机制研究[J].中医药导报,2025,31(2):13-18.
DOI：10.13862/j.cn43-1446/r.2025.02.003
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摘要：目的：研究黄芩苷通过铁死亡途径对H9c2心肌细胞缺氧复氧损伤的作用及机制。方法：采用Na2S2O4诱导大鼠H9c2心肌细胞铁死亡模型，随后用黄芩苷干预。采用试剂盒检测细胞活力、ROS、线粒体膜电位和Fe2+水平。Western blotting检测细胞PTGS2、NOX2和GPX4蛋白表达水平。PTGS2激动剂BUR1联合黄芩苷干预Na2S2O4诱导的细胞后，试剂盒检测细胞Fe2+水平。结果：80 μmol/L以内的黄芩苷对H9c2细胞无毒性。Na2S2O4诱导H9c2细胞铁死亡，表现为细胞ROS和Fe2+水平升高，线粒体膜电位坍塌，GPX4表达明显下降（P<0.05）。黄芩苷干预后，Na2S2O4诱导的细胞ROS和Fe2+水平下降，线粒体膜电位恢复，GPX4表达明显升高（P<0.05），铁死亡进程被逆转。Na2S2O4诱导H9c2细胞后，PTGS2和NOX4表达明显升高（P<0.05），而黄芩苷干预后，Na2S2O4诱导的H9c2心肌细胞PTGS2和NOX4表达明显降低（P<0.05）。黄芩苷与PTGS2和NOX4有很好的结合活性，结合能分别为 -10.65和-8.82 kcal/mol。BUR1能够逆转黄芩苷抑制的Fe2+水平。结论：黄芩苷对Na2S2O4诱导H9c2细胞建立的缺氧复氧损伤模型铁死亡具有明确的恢复作用，其机制可能与其抑制PTGS2和NOX4蛋白表达有关。
关键词：缺血性心肌病；黄芩苷；铁死亡；大鼠H9c2心肌细胞；Na2S2O4；PTGS2；NOX4
Abstract：
Objective: To investigate the effect and mechanism of baicalin on hypoxia-reoxygenation injury in H9c2 cells via regulating ferroptosis. Methods: Rat H9c2 cardiomyocytes hypoxia-reoxygenation injury model was constructed with Na2S2O4, followed by baicalin intervention. Cell viability, ROS, mitochondrial membrane potential, and Fe2+ levels were measured using assay kits. Western blotting was utilized to evaluate cell PTGS2, NOX2, and GPX4 protein expression levels. Cell Fe2+ levels were examined using assay kits after baicalin intervention with PTGS2 agonist BUR1 following Na2S2O4 induction. Results: Baicalin up to 80 μmol/L showed no toxicity to H9c2 cells. Na2S2O4 induced ferroptosis in H9c2 cells, characterized by elevated ROS and Fe2+ levels, mitochondrial membrane potential collapse, and significant decrease in GPX4 expression (P<0.05). Baicalin intervention led to decreased ROS and Fe2+ levels induced by Na2S2O4, restored mitochondrial membrane potential, markedly increased GPX4 expression (P<0.05), and reversing the process of ferroptosis. After Na2S2O4 induction in H9c2 cells, PTGS2 and NOX4 expression significantly increased (P<0.05), while baicalin markedly reduced the expression of PTGS2 and NOX4 induced by Na2S2O4 (P<0.05). Baicalin exhibited good binding activity with PTGS2 and NOX4, with binding energies of -10.65 and -8.82 kcal/mol, respectively. BUR1 could reverse the baicalin-inhibited Fe2+ levels. Conclusion: Baicalin demonstrates a clear therapeutic effect on ferroptosis in the hypoxia-reoxygenation injury model established by Na2S2O4-induced H9c2 cells, and its treatment mechanism may be associated with the inhibition of PTGS2 and NOX4 protein expression.
Key words：ischemic cardiomyopathy; baicalin; ferroptosis, rat H9c2 cardiomyocytes; Na2S2O4; PTGS2; NOX4
发布时间：2025-12-07
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