Wu Fan, Yuan Xiaoling, Liu Weili, Meng Lijun, Li Xiuru, Gao Xiang, Zhou Shuting, Fang Lei, Yu Duonan
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, China.
Ann Transl Med. 2022 May;10(10):538. doi: 10.21037/atm-22-1024.
Sepsis is associated with a high mortality rate. A major cause of death in sepsis patients is respiratory failure, which is characterized by oxidative injury, epithelial apoptosis, and increased lung permeability. MicroRNAs (miRs) are important regulators of sepsis progression.
This study aimed to explore the role of in sepsis in mice. Experimental sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP).
CLP significantly induced systemic inflammation, lung permeability, and lung epithelial apoptosis with downregulated messenger RNA (mRNA) levels of antioxidant enzymes. The knockout mice had a lower 48-hour survival rate, higher plasma tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, and greater pulmonary permeability compared with wild-type mice after CLP. CLP also markedly increased interstitial hemorrhage, collapsed more alveolar sacs, and increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive and Bcl-2-associated X (Bax)-positive cells in knockout lung tissues, with elevated mRNA levels of and reduced activities of catalase (Cat), glutathione peroxidase 1(Gpx1). negatively regulated 14-3-3ζ expression evidenced in knockout lungs and the A549 cell line. In lipopolysaccharide (LPS)-induced A549 cells, overexpression remarkably suppressed the production of reactive oxygen species, inhibited cell apoptosis, and enhanced levels of protein and related enzymes.
Deletion of the cluster aggravated sepsis-induced oxidative injury of lung epithelial cells.
脓毒症与高死亡率相关。脓毒症患者死亡的主要原因是呼吸衰竭，其特征为氧化损伤、上皮细胞凋亡和肺通透性增加。微小RNA（miRs）是脓毒症进展的重要调节因子。
本研究旨在探讨[具体内容缺失]在小鼠脓毒症中的作用。通过盲肠结扎和穿刺（CLP）在C57BL/6小鼠中诱导实验性脓毒症。
CLP显著诱导全身炎症、肺通透性和肺上皮细胞凋亡，同时抗氧化酶的信使核糖核酸（mRNA）水平下调。与野生型小鼠相比，[具体内容缺失]基因敲除小鼠在CLP后48小时生存率较低，血浆肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）水平较高，肺通透性更大。CLP还显著增加了[具体内容缺失]基因敲除肺组织中的间质出血，使更多肺泡囊塌陷，并增加了末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性和Bcl-2相关X蛋白（Bax）阳性细胞的数量，同时[具体内容缺失]的mRNA水平升高，过氧化氢酶（Cat）、谷胱甘肽过氧化物酶1（Gpx1）的活性降低。[具体内容缺失]在[具体内容缺失]基因敲除肺组织和A549细胞系中负向调节14-3-3ζ的表达。在脂多糖（LPS）诱导的A549细胞中，[具体内容缺失]过表达显著抑制活性氧的产生，抑制细胞凋亡，并提高[具体内容缺失]蛋白和相关酶的水平。
[具体内容缺失]簇的缺失加重了脓毒症诱导的肺上皮细胞氧化损伤。
