College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Immunol. 2021 Nov 19;12:767155. doi: 10.3389/fimmu.2021.767155. eCollection 2021.
Stroke is a common central nervous system disease in clinical practice. Stroke patients often have infectious complications, such as pneumonia and infections of the urinary tract and gastrointestinal tract. Although it has been shown that translocation of the host gut microbiota to the lungs and immune dysfunction plays a vital role in the development of infection after ischemic stroke, the occurrence and mechanism of pulmonary infection at different time points after hemorrhagic cerebral remain unclear. In this study, the changes in the immune system and intestinal barrier function in mice during disease development were investigated at 1 day (M 1 d), 3 days (M 3 d) and 7 days (M 7 d) following hemorrhagic stroke to clarify the mechanism of secondary pulmonary infection. The experimental results revealed that after hemorrhagic stroke, model mice showed increased brain damage from day 1 to 3, followed by a trend of brain recovery from day 3 to 7 . After hemorrhagic stroke, the immune system was disturbed in model mice. Significant immunosuppression of the peripheral immune system was observed in the M 3 d group but improved in the M 7 d group. Staining of lung tissues with hematoxylin and eosin (H&E) and for inflammatory factors revealed considerable disease and immune disorders in the M 7 d group. Stroke seriously impaired intestinal barrier function in mice and significantly changed the small intestine structure. From 1 to 7 d after stroke, intestinal permeability was increased, whereas the levels of markers for intestinal tight junctions, mucus and immunoglobulin A were decreased. Analysis based on 16S rRNA suggested that the microflora in the lung and ileum was significantly altered after stroke. The composition of microflora in lung and ileum tissue was similar in the M 7d group, suggesting that intestinal bacteria had migrated to lung tissue and caused lung infection at this time point after hemorrhagic stroke. In stroke mice, the aggravation of intestinal barrier dysfunction and immune disorders after intracerebral hemorrhage, promoted the migration of enteric bacteria, and increased the risk of pneumonia poststroke. Our findings reveal the dynamic process of infection after hemorrhagic stroke and provide clues for the optimal timing of intervention for secondary pulmonary infection in stroke patients.
中风是临床实践中常见的中枢神经系统疾病。中风患者常发生感染性并发症，如肺炎和尿路感染、胃肠道感染。尽管已经表明，宿主肠道微生物群易位到肺部和免疫功能障碍在缺血性中风后感染的发展中起着至关重要的作用，但出血性脑卒后不同时间点肺部感染的发生和机制仍不清楚。在这项研究中，在出血性中风后 1 天（M1d）、3 天（M3d）和 7 天（M7d），研究了疾病发展过程中老鼠免疫系统和肠道屏障功能的变化，以阐明继发性肺部感染的机制。实验结果表明，出血性中风后，模型鼠从第 1 天到第 3 天大脑损伤增加，然后从第 3 天到第 7 天大脑恢复。出血性中风后，模型鼠的免疫系统受到干扰。在 M3d 组观察到外周免疫系统明显免疫抑制，但在 M7d 组得到改善。用苏木精和伊红（H&E）对肺组织进行染色和对炎症因子进行染色，发现 M7d 组疾病和免疫紊乱相当严重。中风严重损害了小鼠的肠道屏障功能，显著改变了小肠结构。中风后 1 至 7 天，肠通透性增加，而肠道紧密连接、粘液和免疫球蛋白 A 的标志物水平降低。基于 16S rRNA 的分析表明，中风后肺部和回肠的微生物群发生了显著变化。M7d 组肺部和回肠组织的微生物群组成相似，提示此时出血性中风后肠道细菌已迁移至肺组织并引起肺部感染。在中风小鼠中，脑出血后肠道屏障功能障碍和免疫紊乱的加重，促进了肠道细菌的迁移，增加了中风后肺炎的风险。我们的发现揭示了出血性中风后感染的动态过程，并为中风患者继发性肺部感染的最佳干预时机提供了线索。
