Platelet-rich plasma ameliorates lipopolysaccharide-induced cardiac injury by inflammation and ferroptosis regulation.
Platelet-rich plasma ameliorates lipopolysaccharide-induced cardiac injury by inflammation and ferroptosis regulation.
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DOI：
10.3389/fphar.2022.1026641
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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脓毒症引起的心肌功能障碍（SIMD）是一种致死性疾病，迄今为止在世界范围内尚无特异性治疗方法。富血小板血浆（PRP）作为一种生物制品，因其多样性和潜在的生物学效应而备受关注。然而，其在脂多糖（LPS）诱导的心脏损伤中的作用尚未得到充分研究。本研究旨在探讨PRP在SIMD中的作用机制。将PRP（30 μL）原位注射到心脏中，并将LPS（10 mg/kg）腹腔内注射到小鼠中。用LPS（1 μg/ml）处理乳鼠心肌细胞24 h。结果表明，与LPS组相比，PRP可显著降低乳酸脱氢酶（LDH）和肌酸激酶MB（CK-MB）水平，改善心功能。此外，PRP还能显著降低脂质过氧化产物丙二醛（MDA）含量，提高超氧化物歧化酶（SOD）活性和谷胱甘肽（GSH）含量，从而减轻LPS诱导的氧化应激。Western blot和qPCR结果表明，PRP处理后，LPS诱导的体内和体外铁凋亡和炎症效应均得到改善。此外，PRP可以减轻erastin诱导的铁凋亡，提高细胞活力。机制上，LPS处理后p-AKT和p-mTOR表达下调，而PRP预处理可逆转这一作用。总之，我们的研究表明，PRP可以通过调节AKT/mTOR信号通路在减轻LPS诱导的心脏损伤中发挥独特的作用。这些发现为治疗SIMD提供了新的治疗方向。
Sepsis-induced myocardial dysfunction (SIMD) is a fatal disease with no specific treatment worldwide to this day. As a biological product, platelet-rich plasma (PRP) has attracted much attention due to its diverse and potential biological effects. However, its role in lipopolysaccharide (LPS)-induced cardiac injury has not been fully investigated. This study aimed to explore the mechanism of PRP in SIMD. PRP (30 µL) was injected in situ into the heart, and LPS (10 mg/kg) was injected intraperitoneally into mice. Neonatal rat cardiomyocytes were treated with LPS (1 μg/ml) for 24 h. The results showed that, compared with the LPS group, PRP significantly decreased the levels of Lactate dehydrogenase (LDH) and Creatine Kinase MB (CK-MB), and improved cardiac function. In addition, PRP markedly decreased the Malonic dialdehyde (MDA) content, and increased the Superoxide dismutase (SOD) activity and Glutathione (GSH) level, demonstrating that PRP alleviated LPS-induced oxidative stress. The Western blot and qPCR results showed that LPS-induced ferroptosis and inflammation effects in vivo and in vitro were ameliorated after PRP treatment. Moreover, PRP can alleviate erastin-induced ferroptosis and improve cell viability. Mechanistically, p-AKT and p-mTOR expressions were down-regulated after treatment with LPS, while PRP pretreatment could reverse this effect. In summary, our study demonstrated that PRP could play a unique role in reducing LPS-induced cardiac injury through regulation of AKT/mTOR signaling pathways. These findings provide a new therapeutic direction for treating SIMD.
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