College of Basic Medical Science, Dalian Medical University, Dalian, China.
Sungen Bioscience Co., Ltd., Guangdong, China.
PLoS One. 2023 Nov 27;18(11):e0294763. doi: 10.1371/journal.pone.0294763. eCollection 2023.
Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.
急性肺损伤（ALI）是一种危及生命的疾病，在重症监护领域受到了相当多的关注。本研究旨在探讨维生素 K2（VK2）在 ALI 中的作用和机制。通过腹腔内注射 7mg/kg LPS 诱导小鼠 ALI，采用 0.2 和 15mg/kg 剂量的 VK2 进行胃内注射。我们发现 VK2 改善了肺病理，降低了髓过氧化物酶（MPO）活性以及 TNF-α 和 IL-6 的水平，并提高了 ALI 小鼠的 IL-10 水平。此外，VK2 通过下调和上调 Caspase-3 和 Bcl-2 的表达分别在细胞凋亡中发挥重要作用。至于进一步的机制探索，我们发现 VK2 抑制了 P38 MAPK 信号通路。我们的结果还表明，VK2 抑制了铁死亡，这表现为 MDA 和铁水平降低，GSH 水平升高，分别上调和下调谷胱甘肽过氧化物酶 4（GPX4）和血红素加氧酶-1（HO-1）的表达。此外，VK2 还通过降低未羧化基质 Gla 蛋白（uc-MGP）和去甲赖氨酸（DES）的水平抑制了弹性蛋白降解。总的来说，VK2 通过抑制 LPS 诱导的炎症、细胞凋亡、铁死亡和弹性蛋白降解，显著缓解了 ALI，使其成为 ALI 的一种有潜力的新型治疗候选物。
