Increased Duodenal Mucosa Infiltration by Mast Cells in Rats with Portal Hypertension

Abstract

Background: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. Aims: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. Methods: Five rats in each group (male Wistar, 230–255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. Results: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 ± 3.16 vs. 18.60 ± 1.52), their diameter (20.09 ± 2.90 vs. 12.61 ± 3.97 µm, p < 0.05) and consequently their total area (12,749.30 ± 2,298.26 vs. 3,455.82 ± 1,702.33 µm²) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 ± 12.88, p < 0.05; 22.92 ± 6.72 µm, p < 0.05 and 51,376.95 ± 43,732.24 µm², p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 ± 1.18 in controls to 10.74 ± 1.47, p < 0.01 and 22.50 ± 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 ± 1.78 vs. 17.40 ± 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 ± 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 ± 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 ± 0.09%, p < 0.01). Conclusions: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.

Gut-Brain Chemokine Changes in Portal Hypertensive Rats

“…1 Chemokine protein levels (optical density, absorbance at 492 nm) of CX3CR1/Fractalkine and CXCR4/SDF-1a in splanchnic system of control (C) and portal hypertensive (PHT) rats at 4 weeks of evolution. *P \ 0.05, **P \ 0.01; Statistically significant values in relation to the control group recruitment and/or proliferation that characterize prehepatic PH in the rat [25,26]. It has recently been proposed that gut-barrier dysfunction related to alterations of gut flora (microbiota) could be the cause of the bacterial translocation to mesenteric lymph nodes produced in TPVL-rats at 1 month of evolution [27].…”

Bacterial Translocation to Mesenteric Lymph Nodes Increases in Chronic Portal Hypertensive Rats

“…Therefore, in TPVL rats the hepatic production of pro-inflammatory mediators could induce harmful effects on the intestinal tract after being released [47,49,50]. However, the existence of an increased infiltration by mast cell in the small bowel and MLN in TPVL rats [51,52] suggests their involvement in the development of portal hypertensive enteropathy and, therefore in BT, through the release of their multiple pro-inflammatory mediators [53][54][55].…”

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

“…Furthermore, in experimental portal hypertensive enteropathy, the increased degree of mast cell infiltration coexists with a higher vessel number in these intestinal layers. Indeed, the number of mast cells shows a positive and statistically significant correlation with the vascular diameter and total microvascular surface [73]. Splanchnic hyperemia, increased splanchnic vascularization, and the development of portal-systemic collateral circulation in experimental portal hypertension are all angiogenic processes that are partly vascular endothelial growth factor (VEGF) dependent [74,75].…”