| 鸢尾素对缺血再灌注心肌铁死亡的抑制作用 |
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| 引用本文： | 李丽,于昊祯,王一石,殷玥,余璐,仝武军. 鸢尾素对缺血再灌注心肌铁死亡的抑制作用[J]. 心脏杂志, 2021, 33(5): 465. DOI: 10.12125/j.chj.202106052 |
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| 作者姓名： | 李丽 于昊祯 王一石 殷玥 余璐 仝武军 |
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| 作者单位： | 1.联勤保障部队临潼康复疗养中心药剂科，陕西 西安 710600 |
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| 基金项目： | 陕西省社发攻关项目资助（2018SF-270） |
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| 摘 要： | 目的 建立小鼠心肌缺血再灌注（MI/R）损伤模型，探讨鸢尾素（irisin）能否抑制心肌铁死亡进而发挥心肌保护作用。 方法 将80只5周龄健康雄性C57小鼠随机分为正常对照组（40只）和运动训练组（40只）。运动组完成训练后进一步将两组小鼠分为假手术组和MI/R组（每组20只）。采用小鼠急性MI/R在体模型(缺血30 min，再灌注24 h) 于再灌注后取心肌组织，检测各组血清及组织中irisin水平、铁死亡相关信号表达、心肌梗死面积和整体心脏功能。在细胞学实验中，采用H9c2心肌细胞建立缺氧/复氧（H/R）模型并给予irisin处理后检测铁死亡相关信号表达情况。 结果 铁死亡抑制剂ferrostatin-1可显著减小MI/R心肌梗死面积，降低MI/R心肌中铁死亡标志物Ptgs2 mRNA和丙二醛（MDA）水平，提示心肌铁死亡是MI/R心肌损伤的重要部分。与对照组相比，有氧运动训练可有效提高骨骼肌和心肌中的irisin水平（P<0.05）。运动组MI/R心肌的铁死亡程度被显著抑制，心肌Ptgs2 mRNA、MDA和脂质过氧化程度均显著降低（P<0.05），心功能显著改善（P<0.05）。外源性补充irisin可有效提高MI/R心肌中GPX4水平而抑制心肌铁死亡程度，减小心肌梗死面积（P<0.05）。细胞学实验发现采用siRNA抑制H9c2细胞整合素αV/β5受体可有效阻断irisin对铁死亡的抑制作用。 结论 鸢尾素通过整合素αV/β5受体-GPX4信号途径抑制MI/R心肌铁死亡。有氧运动训练可通过提高内源性irisin水平实现心肌保护作用。
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| 关 键 词： | 鸢尾素 心肌缺血再灌注损伤 铁死亡 心肌梗死 |
| 收稿时间： | 2021-06-16 |
Irisin alleviates myocardial ischemia-reperfusion injury by inhibiting ferroptosis |
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| Affiliation: | 1.Department of Pharmacy, PLA Lintong Sanitarium, Xi’an 710600, Shaanxi, China2.School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China3.Department of Pathology, School of Basic Medical Sciences, Air Force Medical University, Xi’an 710032, Shaanxi, China |
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| Abstract: | AIM To investigate whether Irisin protects against myocardial ischemia/reperfusion (MI/R) induced ferroptosis in mice. METHODS Eighty healthy male C57 mice aged 5 weeks were randomly divided into a normal control group (40 mice) and an exercise training group (40 mice). After the exercise training, the two groups of mice were further divided into sham group and MI/R group (20 in each group). The in vivo mouse models of myocardial I/R injury were used. After 30 min ischemia and 24 h reperfusion period, heart tissues were excised. The levels of irisin in serum and tissues of each group, the expression of iron death-related signals, and the area of myocardial infarction were measured. Myocardial function was also evaluated. In cytology experiments, in vitro hypoxia/reoxygenation (H/R) injury model for H9C2 cardiomyocytes with irisin treatment were used to detect the expression of ferroptosis-related signals. RESULTS The ferroptosis inhibitor ferrostatin-1 (Fer-1) significantly reduced the MI/R myocardial infarction area and decreased the levels of cardiac Ptgs2 mRNA and MDA, suggesting that myocardial ferroptosis was involved in MI/R injury. Compared with the control group, aerobic exercise training effectively increased the level of irisin in skeletal muscle and myocardium (P<0.05). In addition, the degree of myocardial ferroptosis in the exercise MI/R group was significantly inhibited, manifested as myocardial Ptgs2mRNA, MDA and lipid peroxidation were significantly reduced (P<0.05), while cardiac function was significantly improved (P<0.05). Exogenous supplementation of irisin effectively increased the level of GPX4 in MI/R myocardium, inhibited myocardial ferroptosis, and reduced the area of myocardial infarction (P<0.05). Cytological experiments found that irisin-induced ferroptosis inhibition was effectively blocked by knockdown of integrin αV/β5 receptor using siRNA. CONCLUSION Irisin inhibits MI/R myocardial ferroptosis through the integrin αV/β5 -GPX4 signaling pathway. Aerobic exercise training achieves cardioprotection by increasing the level of endogenous irisin. |
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