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.

Keywords: Acute lung injury; HMGB1; Mesenteric lymph; Severe acute pancreatitis.

Fig. 1

Impacts of MLDL on STC-induced pancreatic injury. a Images of H&E staining, 200 × magnifications of pancreas tissues of each experimental group. b Pathological score of pancreas tissues of each experimental group. ***p < 0.001, compared with the SO group; #p < 0.05, compared with the SAP group. n = 10–14

Fig. 2

Impacts of MLDL on SAP-associated lung injury. a Images of H&E staining, 200 × magnifications of lung tissues of each experimental group. b Pathological score of lung tissues of each experimental group. c MPO activity in lung tissues of each experimental group. ***p < 0.001, compared with the SO group; #p < 0.05, compared with the SAP group. n = 10–14

Fig. 3

Impacts of MLDL on SAP-associated intestinal injury. a Images of intestinal tissues H&E staining of each experimental group (200 × magnifications). b Pathological score of intestinal tissues of each experimental group. c Serum D-LA levels of each experimental group. d Serum DAO levels of each experimental group. ***p < 0.001, compared with the SO group; #p < 0.05, compared with the SAP group. n = 10–14

Fig. 4

Impacts of MLDL on the expressions of HMGB1, RAGE, and NF-κB p65 at the mRNA and protein levels in lung tissues. a RT-PCR analysis of HMGB1, RAGE, and NF-κB p65 mRNA expression in lung tissues. b Western blot results of HMGB1, RAGE, and NF-κB p65 protein expression in lung tissues. c Statistical results of B scanning densitometry. ***p < 0.001, compared with the SO group; #p < 0.05, compared with the SAP group. n = 10–14

Fig. 5

Impacts of MLDL on the levels of inflammatory factors in serum and intestinal lymphoid tissues. a ELISA data of TNF-α, IL-6 and ICAM1 in serum; b RT-PCR analysis of HMGB1, RAGE and TNF-α mRNA in intestinal lymphoid tissues. ***p < 0.001, compared with the SO group; #p < 0.05, ##p < 0.01, compared with the SAP group. n = 10–14