目的 探讨消瘀降脂胶囊对过氧化氢（hydrogen peroxide，H₂O₂）诱导的H9c2心肌细胞损伤的保护作用及其作用机制。方法 采用H₂O₂诱导H9c2细胞构建氧化损伤模型，设置对照组、模型组和消瘀降脂胶囊（75、150、300 μg/mL）组，给予药物进行干预。通过CCK-8法检测细胞存活率；检测氧化应激指标乳酸脱氢酶（lactate dehydrogenase，LDH）、超氧化物歧化酶（superoxide dismutase，SOD）活性及丙二醛（malondialdehyde，MDA）水平；流式细胞术测定细胞内活性氧（reactive oxygen species，ROS）水平；Western blotting检测核因子E2相关因子2（nuclear factor E2 related factor 2，Nrf2）、血红素加氧酶-1（heme oxygenase 1，HO-1）、磷酸化细胞外调节蛋白激酶（phosphorylated extracellular regulated protein kinases 1/2，p-ERK1/2）、磷酸化p38（phosphorylated p38，p-p38）和磷酸化c-Jun氨基末端激酶（phosphorylated c-Jun N-terminal kinase，p-JNK）蛋白表达。结果 与模型组比较，消瘀降脂胶囊呈剂量相关性地提高H₂O₂诱导的H9c2细胞存活率（P＜0.05、0.01），降低细胞内ROS蓄积（P＜0.001），显著抑制LDH活性及MDA水平（P＜0.001），显著提高SOD活性（P＜0.001）。Western blotting结果显示，经消瘀降脂胶囊干预后，Nrf2及其下游HO-1蛋白表达水平均显著升高（P＜0.01、0.001），p-ERK1/2水平显著升高（P＜0.05、0.01），而p-p38水平显著降低（P＜0.01、0.001），p-JNK水平无显著变化。结论 消瘀降脂胶囊通过调控丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）-Nrf2/抗氧化反应元件（antioxidant response element，ARE）信号通路重建氧化还原稳态，从而减轻心肌细胞氧化损伤。

Objective To investigate the protective effect and mechanism of Xiaoyu Jiangzhi Capsules (消瘀降脂胶囊) on hydrogen peroxide (H₂O₂)-induced H9c2 cardiomyocytes injury. Methods The oxidative injury model was constructed using H₂O₂-treated H9c2 cardiomyocytes, control group, model group, Xiaoyu Jiangzhi Capsules (75, 150, 300 μg/mL) groups were set up, drugs were given for intervention. Cell survival rate was detected by CCK-8 assay. Oxidative stress indicators lactate dehydrogenase (LDH), superoxide dismutase (SOD) activities and malondialdehyde (MDA) level were detected. Intracellular reactive oxygen species (ROS) level were measured by flow cytometry. Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), phosphorylated extracellular regulated protein kinases 1/2 (p-ERK1/2), phosphorylated p38 (p-p38) and phosphorylated c-Jun N-terminal kinase (p-JNK) protein expressions were detected by Western blotting. Results Compared with model group, Xiaoyu Jiangzhi Capsules showed a dose-dependent increase in H₂O₂-induced H9c2 cell survival rate (P < 0.05, 0.01), decreased intracellular ROS accumulation (P < 0.001), significantly inhibited LDH activity and MDA level (P < 0.001), and significantly increased SOD activity (P < 0.001). Western blotting results showed that after intervention with Xiaoyu Jiangzhi Capsules, the expression levels of Nrf2 and its downstream HO-1 protein were significantly increased (P < 0.01, 0.001), the level of p-ERK1/2 was significantly increased (P < 0.05, 0.01), while the level of p-p38 was significantly decreased (P < 0.01, 0.001), and the level of p-JNK showed no significant change. Conclusion Xiaoyu Jiangzhi Capsules could reduce cardiomyocyte oxidative damage by regulating mitogen-activated protein kinase (MAPK)-Nrf2/antioxidant response element (ARE) signaling pathway to restore redox homeostasis.

R285.5