Bardoxolone Methyl 通过激活 Nrf2/HO-1 信号通路减轻心肌缺血/再灌注损伤。
Bardoxolone Methyl Ameliorates Myocardial Ischemia/Reperfusion Injury by Activating the Nrf2/HO-1 Signaling Pathway.
机构信息
Department of Cardiology, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China.
Institute of Translational Medicine, Shanghai University, Shanghai, China.
出版信息
Cardiovasc Ther. 2023 Feb 22;2023:5693732. doi: 10.1155/2023/5693732. eCollection 2023.
BACKGROUND
Myocardial ischemia/reperfusion (I/R) injury is a severe heart problem resulting from restoring coronary blood flow to the myocardium after ischemia. This study is aimed at ascertaining the therapeutic efficiency and action mechanism of bardoxolone methyl (BARD) in myocardial I/R injury.
METHODS
In male rats, myocardial ischemia was performed for 0.5 h, and then, reperfusion lasted for 24 h. BARD was administrated in the treatment group. The animal's cardiac function was measured. Myocardial I/R injury serum markers were detected via ELISA. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to estimate the infarction. H&E staining was used to evaluate the cardiomyocyte damage, and Masson trichrome staining was used to observe the proliferation of collagen fiber. The apoptotic level was assessed via the caspase-3 immunochemistry and TUNEL staining. Oxidative stress was measured through malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, and inducible nitric oxide synthases. The alteration of the Nrf2/HO-1 pathway was confirmed via western blot, immunochemistry, and PCR analysis.
RESULTS
The protective effect of BARD on myocardial I/R injury was observed. In detail, BARD decreased cardiac injuries, reduced cardiomyocyte apoptosis, and inhibited oxidative stress. For mechanisms, BARD treatment significantly activates the Nrf2/HO-1 pathway.
CONCLUSION
BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.
背景
心肌缺血/再灌注（I/R）损伤是一种严重的心脏问题，是由于缺血后恢复心肌的冠状动脉血流而导致的。本研究旨在确定 bardoxolone 甲基（BARD）在心肌 I/R 损伤中的治疗效果和作用机制。
方法
雄性大鼠进行 0.5 h 的心肌缺血，然后再灌注 24 h。在治疗组中给予 BARD。测量动物的心脏功能。通过 ELISA 检测心肌 I/R 损伤血清标志物。使用 2,3,5-三苯基氯化四氮唑（TTC）染色评估梗死情况。使用 H&E 染色评估心肌细胞损伤，使用 Masson 三色染色观察胶原纤维的增殖。通过 caspase-3 免疫组化和 TUNEL 染色评估凋亡水平。通过丙二醛、8-羟基-2'-脱氧鸟苷、超氧化物歧化酶和诱导型一氧化氮合酶测量氧化应激。通过 Western blot、免疫化学和 PCR 分析证实 Nrf2/HO-1 通路的改变。
结果
BARD 对心肌 I/R 损伤具有保护作用。具体来说，BARD 降低了心脏损伤，减少了心肌细胞凋亡，并抑制了氧化应激。对于机制，BARD 治疗显著激活了 Nrf2/HO-1 通路。
结论
BARD 通过激活 Nrf2/HO-1 通路抑制氧化应激和心肌细胞凋亡来改善心肌 I/R 损伤。
Zotero 插件