Intensive Care Unit, Tianjin Nankai Hospital, 6 Changjiang Road, Nankai District, Tianjin, 300100, China,
Inflammation. 2015;38(3):1239-49. doi: 10.1007/s10753-014-0091-z.
The purpose of this study is to investigate the hypothesis that the mesenteric lymphatic system plays an important role in acute lung injury in a rat model induced by severe intraperitoneal infection. Male Wistar rats weighing 250∼300 g were randomly divided into 3 groups and subjected to sham operation, intraperitoneal infection, or mesenteric lymphatic drainage. The activity of diamine oxidase (DAO) and myeloperoxidase (MPO) were measured by enzymatic assay. The endotoxin levels in plasma, lymph, and bronchoalveolar lavage fluid (BALF) were evaluated using the limulus amoebocyte lysate reagent. The cytokines, adhesion factors, chemokines, and inflammatory factors were detected by ELISA. TLR-4, NF-kB, and IRAK-4 were analyzed by Western blotting. Compared with sham-operated rats, rats with intraperitoneal infection had increased MPO and decreased DAO activity in intestinal tissues. Mesenteric lymph drainage reduced the alterations in MPO and DAO activity induced by intraperitoneal infection. The MPO activity in pulmonary tissue and the permeability of pulmonary blood vessels were also increased, which were partially reversed by mesenteric lymph drainage. The endotoxin levels in lymphatic fluid and alveolar perfusion fluid were elevated after intraperitoneal infection but decreased to control levels after lymph drainage. No alterations in the levels of plasma endotoxin were observed. The number of neutrophils was increased in BALF and lymph in the infected rats, and was also reduced after drainage. Lymph drainage also decreased the levels of inflammatory cytokines, chemokines, and adhesion factors in the plasma, lymph, and BALF, as well as the levels of TLR-4, NF-kB, and IRAK-4 in pulmonary and intestinal tissues. The mesenteric lymphatic system is the main pathway involved in early lung injury caused by severe intraperitoneal infection, in which activation of the TLR-4 signal pathway may play a role.
本研究旨在探讨肠系膜淋巴系统在大鼠严重腹腔感染致急性肺损伤中的作用。雄性 Wistar 大鼠 250∼300 g 随机分为 3 组，行假手术、腹腔感染或肠系膜淋巴引流术。酶联免疫吸附试验（ELISA）测定二胺氧化酶（DAO）和髓过氧化物酶（MPO）活性。鲎试验检测血浆、淋巴和支气管肺泡灌洗液（BALF）内毒素水平。ELISA 检测细胞因子、黏附因子、趋化因子和炎症因子。Western blot 分析 TLR-4、NF-kB 和 IRAK-4。与假手术组比较，腹腔感染组大鼠肠组织 MPO 活性增加，DAO 活性降低。肠系膜淋巴引流可减轻腹腔感染引起的 MPO 和 DAO 活性改变。肺组织 MPO 活性和肺血管通透性增加，肠系膜淋巴引流可部分逆转。腹腔感染后淋巴液和肺泡灌洗液内毒素水平升高，引流后降至对照水平。血浆内毒素水平无变化。感染组大鼠 BALF 和淋巴液中中性粒细胞数增加，引流后减少。淋巴引流还可降低血浆、淋巴和 BALF 中炎症因子、趋化因子和黏附因子的水平，以及肺和肠组织中 TLR-4、NF-kB 和 IRAK-4 的水平。肠系膜淋巴系统是严重腹腔感染致早期肺损伤的主要途径，其中 TLR-4 信号通路的激活可能发挥作用。
