DNaseI protects lipopolysaccharide-induced endometritis in mice by inhibiting neutrophil extracellular traps formation
DNaseI protects lipopolysaccharide-induced endometritis in mice by inhibiting neutrophil extracellular traps formation
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DNaseI 通过抑制中性粒细胞胞外陷阱的形成来保护脂多糖诱导的小鼠子宫内膜炎
DOI：
10.1016/j.micpath.2020.104686
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发表时间：
2021-01-01
影响因子：
3.8
通讯作者：
Fu, Yunhe
中科院分区：
文献类型：
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作者：
Hao, Haoyang;Yu, Huiyuan;Fu, Yunhe
子宫内膜炎是由细菌感染引起的子宫内膜炎症，影响人类和动物的女性生殖健康。神经细胞外陷阱（NETs）具有抵抗病原体入侵引起的感染的能力。研究表明，NETs的形成与某些炎症性疾病有关，如乳腺炎和慢性阻塞性肺疾病（COPD）。然而，有稀疏的研究与NET和神经胶质瘤。在这项研究中，我们研究了NET在脂多糖（LPS）诱导的小鼠急性肠炎中的作用，并评估了DNaseI的治疗效果。我们建立了LPS诱导的小鼠子宫内膜炎模型，发现在小鼠体内子宫组织中可以检测到NETs的形成。此外，DNaseI处理可以抑制LPS诱导的小鼠腹膜炎中NETs的构建。髓过氧化物酶（MPO）活性测定表明DNaseI处理显著减轻炎症细胞浸润。酶联免疫吸附试验表明DNaseI处理显著抑制促炎细胞因子TNF-α和IL-1 β的表达。此外，发现DNaseI增加子宫组织紧密连接的蛋白质表达并抑制LPS诱导的NF-κ B活化。上述结果表明，DNaseI通过阻断NF-κ B B信号通路，有效抑制NET的形成，并促进紧密连接蛋白的表达，从而减轻LPS诱导的炎症反应。
Endometritis is an inflammatory of the inner lining of the uterus caused by bacterial infections that affect female reproductive health in humans and animals. Neutrophil extracellular traps (NETs) have the ability to resist infections that caused by pathogenic invasions. It has been proved that the formation of NETs is related to certain inflammatory diseases, such as mastitis and chronic obstructive pulmonary disease (COPD). However, there are sparse studies related to NETs and endometritis. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-induced acute endometritis in mice and evaluated the therapeutic efficiency of DNaseI. We established LPS-induced endometritis model in mice and found that the formation of NETs can be detected in the mice uterine tissues in vivo. In addition, DNaseI treatment can inhibit NETs construction in LPS-induced endometritis in mice. Moreover, myeloperoxidase (MPO) activity assay indicated that DNaseI treatment remarkably alleviated the inflammatory cell infiltrations. ELISA test indicated that the treatment of DNaseI significantly inhibited the expression of the proinflammatory cytokines TNF-alpha, and IL-1 beta. Also, DNaseI was found to increase proteins expression of the uterine tissue tight junctions and suppress LPS-induced NF-kappa B activation. All the results indicated that DNaseI effectively inhibits the formation of NETs by blocking the NF-kappa B signaling pathway and enhances the expression of tight junction proteins, consequently, alleviates inflammatory reactions in LPS-induced endometritis in mice.