GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage.
GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage.
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DOI：
10.1155/2021/5589472
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发表时间：
2021
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Liu Y;Zhang Y;Feng Q;Liu Q;Xie J;Li H;Yang F;Liu X;Gao W;Bai X;Li Z;Wang Y
急性肺损伤（acute lung injury，ALI）是一种严重的呼吸道感染，由于缺乏有效的治疗，是重症监护中死亡率的重要因素。炎症、氧化应激和焦亡与多种炎性疾病如ALI相关。Gly-Pro-Ala（GPA）肽在各种炎症性疾病中调节氧化应激和细胞凋亡已被公认。本研究旨在探讨GPA多肽对急性肺损伤的调节作用和保护作用。在本研究中，盲肠结扎和穿孔（CLP）技术被用来诱发脓毒症的小鼠，并在CLP后腹腔内给予不同浓度（50，100，和150 mg/kg）的GPA肽。记录肺组织病理学变化及肺湿/干比值。我们还研究了氧化应激、炎症和焦亡的水平。结果显示，GPA肽显著改善CLP刺激的肺组织损伤，抑制促炎细胞因子释放，减少炎性细胞浸润。此外，GPA肽抑制肺泡巨噬细胞中的氧化应激和半胱天冬酶-1依赖的焦亡。此外，我们的研究表明，GPA肽防止肺泡巨噬细胞通过减弱ROS发生焦亡。结果表明，GPA肽通过抑制氧化应激和肺泡巨噬细胞凋亡对CLP诱导的ALI具有保护作用。
Acute lung injury (ALI) has been known to be a devastating form of respiratory infection and an important contributor to mortality in intensive care, due to its lacking of effective treatment. Inflammation, oxidative stress, and pyroptosis are associated with multiple kinds of inflammatory diseases such as ALI. It is commonly accepted that Gly-Pro-Ala (GPA) peptide regulates oxidative stress and pyroptosis in different kinds of inflammatory diseases. Our study is aimed at exploring the regulatory function and protective effects of GPA peptides on ALI. In the current study, the cecal ligation and puncture (CLP) technique was used to evoke sepsis in mice, and GPA peptide was administered intraperitoneally with different concentrations (50, 100, and 150 mg/kg) after CLP. Histopathological changes and the ratio of wet-to-dry in lung were recorded and analyzed. We also investigated the level of oxidative stress, inflammation, and pyroptosis. Results showed that GPA peptide significantly ameliorated CLP-stimulated lung tissue injury, impeded proinflammatory cytokine release, and reduced inflammatory cell infiltration. Additionally, GPA peptide suppressed oxidative stress and caspase-1-dependent pyroptosis in alveolar macrophages. Furthermore, our study showed that the GPA peptide prevents alveolar macrophage from undergoing pyroptosis by attenuating ROS. In conclusion, results demonstrated that GPA peptide has protective effects in CLP-stimulated ALI by inhibiting oxidative stress as well as pyroptosis of alveolar macrophage.
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