PDF(Pubmed)
Abstract：
Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.
摘要：
塑料支气管炎（PB）构成危及生命的肺部疾病，主要归因于肺炎支原体（MP）感染。所涉及的致病机制在很大程度上仍未被探索，导致缺乏可靠的早期诊断和明确治疗方法。因此，本研究旨在建立MP诱导的PB小鼠模型，从而增强我们对这种复杂情况的理解。在第一阶段,健康BALB/c小鼠用于研究建立PB的最佳方法。这涉及使用浓度为4.5％至7.5％的2-氯乙基乙基硫醚（CEES）进行雾化（15-20分钟）和气管内给药（6-50μL）。随后，MP模型是通过施用MP溶液(2mL/kg/天，108CFU/50μL）通过鼻内途径，持续连续五天。最终,在MP模型中采用合适的技术诱导塑性支气管炎。分析肺组织病理变化，和免疫组织化学方法确定血管内皮生长因子受体3（VEGFR-3）和PI3K/AKT/mTOR信号通路的表达水平。通过6μL气管施用4.5％CEES是建立PB模型的最佳方法。该方法主要诱导嗜中性粒细胞炎症和纤维蛋白渗出物。MP感染组表现出提示呼吸道感染的症状，包括直立的头发，口腔和鼻腔分泌物，和体重的下降。此外，MP+CEES组的病理评分分别超过接受MP或CEES治疗的组。值得注意的是,MP+CEES组显示VEGFR-3和PI3K/AKT/mTOR信号通路的显著激活,暗示在这种病理中淋巴管损伤的实质性参与。本研究采用两步法成功建立了MP诱导PB的小鼠模型。淋巴管损伤是该疾病实体的致病机制中的关键要素。这一成就将有助于进一步研究MP引起的PB患者的治疗方法。
