Mesenteric Lymph Duct Ligation Alleviates Acute Lung Injury Caused by Severe Acute Pancreatitis Through Inhibition of High Mobility Group Box 1-Induced Inflammation in Rats

Abstract

Background Acute lung injury (ALI) is the most common complication and one of the leading causes of mortality of severe acute pancreatitis (SAP). Nevertheless, no effective therapeutic schemes are presently available. Aims To investigate the effect and potential mechanism of mesenteric lymph duct ligation (MLDL) on experimental SAP-induced ALI. Methods Immediately following MLDL, rats were subjected to SAP by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. At 24 h after modeling, tissues were collected for morphological examination. The levels of TNF-α, IL-6, intercellular adhesion molecule-1 (ICAM1), diamine oxidase (DAO), and D -lactic acid ( D -LA) in serum, and the myeloperoxidase (MPO) activity in lung tissues were determined. Moreover, the expressions of high mobility group box 1 (HMGB1), receptor of advanced glycation endproducts (RAGE), and NF-κB p65 at the mRNA and protein levels in lung tissues, and the expressions of HMGB1, RAGE, and TNF-α at the mRNA level in intestinal lymphoid tissues were evaluated. Results MLDL significantly attenuated the histological injury of the pancreas and lung and reduced the production of TNF-α, IL-6, and ICAM1. Besides, MLDL repressed the activity of MPO in the lung. However, the levels of serum DAO and D -LA were decreased without obvious morphological improvement in intestinal injury. Moreover, MLDL apparently reduced the up-regulation of HMGB1, RAGE, and NF-κB p65 in lung tissues, as well as the expressions of HMGB1, RAGE, and TNF-α in intestinal lymphoid tissues. Conclusions Mesenteric lymph was a source of harmful factors leading to SAP-ALI. MLDL could alleviate SAP-ALI probably by inhibiting HMGB1-induced production of inflammation factors. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-020-06801-6.

Dynamic Monitoring of Immunoinflammatory Response Identifies Immunoswitching Characteristics of Severe Acute Pancreatitis in Rats

“…The intestinal mucosal barrier function helps maintain intestinal homeostasis ( 25 ). As an intestinal metabolite, the serum D-lactate level can reflect the changes in intestinal mucosal permeability ( 7 , 17 ). The changes in intestinal mucosal barrier function of SAP rats can be determined by observing pathological changes in the small intestines and detecting the serum D-lactate level.…”

“…Rats were fasted for 12 h and anesthetized with 2.0% sodium pentobarbital (Sinopharm Chemical Reagent Co., Ltd., China). The animal model was established according to existing studies ( 17 , 18 ). In brief, an abdominal incision was made along the midline to expose the biliopancreatic duct, and the liver hilum was temporarily closed with a microvascular clamp.…”

Cervical sympathetic trunk transection alleviates acute lung injury caused by intestinal obstruction via inhibition of phospholipase A2 in rats

“…The serum concentrations of chemokines, TNF-α, IL-6, and IL-10 were determined using an enzyme-linked immunosorbent assay (ELISA) kit (Neobioscience, Nanjing Proteinbio Technology Co., Ltd., China) according to the manufacturer’s instructions [ 12 ]. The plates were read using a microplate reader at a wavelength of 450 nm [ 13 ].…”

Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis

“…Recent evidence indicates that HMGB1 participates in pancreatic, intestinal and lung injury during AP (Luan et al, 2013;Chen et al, 2017;Huang et al, 2019). Based on these effects, some new therapeutic approaches, such as calycosin and mesenteric lymph duct ligation to alleviate acute lung injury and euphorbia kansui to restore intestinal mucosa in severe AP were recently studied Qiu et al, 2021;Tang et al, 2021;Zhu et al, 2021). In an experimental AP model, macrophage-derived HMGB1 served as a pain mediator in the early stage of AP (Irie et al, 2017).…”