Lin Fengxia, Xu Luhua, Huang Meizhu, Deng Bin, Zhang Weiwei, Zeng Zhicong, Yinzhi Song
Department of Cardiology, Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, The Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen 518133, China.
Evid Based Complement Alternat Med. 2020 Mar 28;2020:2679409. doi: 10.1155/2020/2679409. eCollection 2020.
Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of -sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential. -Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover, -sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPARγ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes. Furthermore, inhibition of PPARγ impaired the protective actions of -sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats, -sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPARγ. In conclusion, our results demonstrate that -sitosterol protected against H/R-induced cardiomyocyte injury and myocardial I/R injury. The -sitosterol-mediated cardioprotective effects may involve the modulation of PPAR/NF-B signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of -sitosterol in the myocardial I/R injury.
心肌缺血/再灌注（I/R）损伤是一种临床上严重的并发症，尤其在心肌梗死患者中可导致高致残率和死亡率，然而这一过程的分子机制仍不清楚。本研究旨在探讨β-谷甾醇对心肌I/R损伤的保护作用，并阐明其潜在的分子机制。我们的结果表明，缺氧/复氧（H/R）处理抑制细胞活力，诱导细胞凋亡和活性氧生成，增加半胱天冬酶-3和-9活性，上调半胱天冬酶-3和-9蛋白表达，下调Bcl-2蛋白表达，并降低线粒体膜电位。β-谷甾醇处理减轻了H/R诱导的心肌细胞损伤。此外，β-谷甾醇处理抵消了H/R处理对过氧化物酶体增殖物激活受体γ（PPARγ）表达的抑制作用，并增强了H/R处理对心肌细胞中核因子κB（NF-κB）表达的影响。此外，抑制PPARγ会削弱β-谷甾醇对H/R诱导的心肌细胞损伤的保护作用。在I/R大鼠中，β-谷甾醇处理减小了心肌梗死面积并减少了细胞凋亡，而抑制PPARγ会减弱这种作用。总之，我们的结果表明，β-谷甾醇可保护心肌细胞免受H/R诱导的损伤以及心肌I/R损伤。β-谷甾醇介导的心脏保护作用可能涉及在心肌I/R损伤过程中对PPAR/NF-κB信号通路的调节。需要进一步研究以进一步探索β-谷甾醇在心肌I/R损伤中的临床应用。
