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DNaseI 通过抑制中性粒细胞胞外诱捕网的形成来保护 LPS 诱导的小鼠子宫内膜炎。

DNaseI protects lipopolysaccharide-induced endometritis in mice by inhibiting neutrophil extracellular traps formation.

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, PR China.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, PR China.

出版信息

Microb Pathog. 2021 Jan;150:104686. doi: 10.1016/j.micpath.2020.104686. Epub 2020 Dec 11.

Abstract

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-α, and IL-1β. Also, DNaseI was found to increase proteins expression of the uterine tissue tight junctions and suppress LPS-induced NF-κB activation. All the results indicated that DNaseI effectively inhibits the formation of NETs by blocking the NF-κB signaling pathway and enhances the expression of tight junction proteins, consequently, alleviates inflammatory reactions in LPS-induced endometritis in mice.

摘要

子宫内膜炎是一种由细菌感染引起的子宫内层炎症,会影响人类和动物的生殖健康。中性粒细胞胞外诱捕网(NETs)具有抵抗由病原体入侵引起的感染的能力。已经证明,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,与 NETs 和子宫内膜炎相关的研究很少。在这项研究中,我们研究了 NETs 在脂多糖(LPS)诱导的小鼠急性子宫内膜炎中的作用,并评估了 DNaseI 的治疗效果。我们在小鼠中建立了 LPS 诱导的子宫内膜炎模型,发现 NETs 的形成可以在体内小鼠子宫组织中检测到。此外,DNaseI 治疗可以抑制 LPS 诱导的子宫内膜炎中 NETs 的构建。此外,髓过氧化物酶(MPO)活性测定表明,DNaseI 治疗显著减轻了炎症细胞浸润。ELISA 检测表明,DNaseI 处理显著抑制了促炎细胞因子 TNF-α和 IL-1β的表达。此外,还发现 DNaseI 增加了子宫组织紧密连接蛋白的表达,并抑制了 LPS 诱导的 NF-κB 激活。所有结果表明,DNaseI 通过阻断 NF-κB 信号通路有效抑制 NETs 的形成,增强紧密连接蛋白的表达,从而减轻 LPS 诱导的小鼠子宫内膜炎中的炎症反应。

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