分离式氨基酸烯减轻心肌缺血 - 再灌注损伤

Deshan Yao

Ischemia-reperfusion (I/R) injury, a multifaceted pathological process, occurs when the prolongation of reperfusion duration triggers铁凋亡介导的心肌损伤。甘草中的单一类黄酮分离菌素（ISL）表现出广泛的药理影响，但其在心肌I/R损伤引起的铁铁作用中的功能尚不清楚。这项研究深入研究了ISL对心肌I/R损伤引起的铁铁毒死的保护作用及其机械SM。新生小鼠心肌细胞（NMCM）进行了缺氧/re氧（H/R），以模拟心肌I/R的病理过程。 ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage. CCK8实验表明，铁蛋白抑制剂ferrostatin-1显着改善了24小时的氧化后心肌细胞活力，ISL处理显示出相似的作用。 ISL降低了细胞内无铁的积累，上调的谷胱甘肽过氧化物酶4（GPX4）和溶质载体家族7成员11（SLC7A11）表达，并抑制脂质过氧化的积累，从而减轻了脂肪吞噬作用。 NRF2特异性抑制剂ML385应对对H/R触发的氧化应激损伤和铁铁作用的防御作用。 In vivo experiments further confirmed that by regulating the translocation of Nrf2 into the nucleus, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4, Drp1 to exert the antioxidant role, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R. ML385几乎通过抑制NRF2功能，几乎消除了对I/R模型的ISLS保护作用。总而言之，ISL能够减轻氧化应激，线粒体损伤和由I/R引起的心肌细胞性胞菌病，从而减少心肌损伤。一个关键机制包括触发NRF2/HO-1/SLC7A11/GPX4途径，以防止由I/R。