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The Mesenteric Lymph Duct Cannulated Rat Model: Application to the Assessment of Intestinal Lymphatic Drug Transport
Published on: March 6, 2015
Mesenteric lymph duct drainage attenuates acute lung injury in rats with severe intraperitoneal infection
Yanmin Zhang1, Shukun Zhang, Naiqiang Tsui
1Intensive Care Unit, Tianjin Nankai Hospital, 6 Changjiang Road, Nankai District, Tianjin, 300100, China, summer9531@163.com.
Abstract:
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.
Insights
Severe infection triggers acute lung injury via the mesenteric lymphatic system. Draining mesenteric lymph reduces inflammatory markers and protects lung function, highlighting the lymphatic system
Area of Science:
- Pathophysiology
- Gastroenterology
- Pulmonology
Background:
- Intraperitoneal infection can lead to systemic inflammatory responses.
- The role of the mesenteric lymphatic system in mediating acute lung injury (ALI) is not fully understood.
- Severe infections may impact organ crosstalk and inflammatory mediator transport.
Purpose of the Study:
- To investigate the role of the mesenteric lymphatic system in ALI development following severe intraperitoneal infection in a rat model.
- To determine if mesenteric lymphatic drainage can mitigate ALI.
- To explore the involvement of the Toll-like receptor 4 (TLR-4) signaling pathway.
Main Methods:
- Rats underwent sham operation, intraperitoneal infection, or mesenteric lymphatic drainage.
- Assessed diamine oxidase (DAO) and myeloperoxidase (MPO) activity in intestinal and lung tissues.
- Measured endotoxin levels in plasma, lymph, and bronchoalveolar lavage fluid (BALF).
- Quantified cytokines, chemokines, adhesion factors, and TLR-4 pathway components (NF-kB, IRAK-4) using ELISA and Western blotting.
Main Results:
- Intraperitoneal infection increased intestinal MPO and decreased DAO activity, which was reversed by lymph drainage.
- Pulmonary MPO activity and vascular permeability increased post-infection but were partially reduced by lymph drainage.
- Endotoxin and neutrophil levels in lymph and BALF decreased with mesenteric lymph drainage.
- Lymph drainage reduced systemic inflammatory markers and TLR-4 pathway activation in lung and intestinal tissues.
Conclusions:
- The mesenteric lymphatic system serves as a primary conduit for early lung injury following severe intraperitoneal infection.
- Mesenteric lymphatic drainage demonstrates a protective effect against ALI.
- Activation of the TLR-4 signaling pathway is implicated in the pathogenesis of infection-induced ALI via the mesenteric lymphatics.

