Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer

Oh, Tae Young; Ahn, Byung Ok; Jang, Eun Jung; Park, Joo Sang; Park, Sang Jong; Baik, Hyun Wook; Hahm, Ki‐Baik

doi:10.3164/jcbn.2008030

Cited by 23 publications

(8 citation statements)

References 32 publications

(39 reference statements)

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“…Groups II, III, and IV were then treated with mice recombinant human interleukin-1β (IL-1β; 200 μg/kg) respectively for 48 h from day 7 to induce the recurrence of colitis according to the method reported previously with modifications. [ 18 , 19 ] IL-1β produced by inflammatory cells has various biological activities. Infiltrating neutrophils recruited by adhesion molecules are up-regulated by IL-1β, which is closely related to the recurrence of colitis.…”

Section: Methodsmentioning

confidence: 99%

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice

Feng

Fang

Zhao

et al. 2020

Chinese Medical Journal

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Background Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. Methods Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence. Results Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% ( P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% ( P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group. Conclusions These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

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Section: Methodsmentioning

confidence: 99%

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice

Feng

Fang

Zhao

et al. 2020

Chinese Medical Journal

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“…Biochemical studies were then performed using full thickness of intestinal wall in the distal colonic samples. The study of colitis recurrence was conducted according to the methods reported previously with modifications (Watanabe et al, 1997 ; Young Oh et al, 2008 ). Briefly, the recurrence of colitis after SASP or Sal B treatment was induced by giving rats recombinant human IL-1β (150 μg/kg) intraperitoneally for 48 h from day 15.…”

Section: Methodsmentioning

confidence: 99%

Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model

et al. 2016

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Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease.

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“… 5 The gastric mucosa is exposed to acid and other chemical hazards, including food intake, assuming that there is a high chance to receive several challenges during ulcer healing. In the acetic acid–induced ulcer rodent model, several reports have shown that administration of nonsteroidal anti-inflammatory drugs or H pylori causes an ulcer in the area where the initial ulcer had healed, 10 , 39 , 40 although why an offense-induced relapse ulcer occurs at the same site or near the site still is unknown. In the present study, we observed that H pylori causes ulcer relapse, specifically at the site of visually healed regenerated epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies in rodents observed prominent histologic and structural abnormalities in visually healed tissue at least 28 weeks after ulcer induction, including poor differentiation and/or degenerative changes in glandular cells, increased connective tissue, and disorganized microvascular arrays. 1 , 3 , 10 Moreover, in the gastric glands of healed ulcer tissue an up-regulation of trefoil factor 2 (TFF2) and mucin (MUC)6 is accompanied by a lack of parietal cells, 11 , 12 similar to the metaplastic state identified as a precursor of gastric cancer. 12 , 13 , 14 Interestingly, mice with genetic disruption of the Na/H exchanger isoform sodium hydrogen exchanger 2 (NHE2) have atrophied parietal cells with up-regulation of TFF2, 15 , 16 and it has been shown that NHE2 is a downstream mediator of TFF2 for the gastric repair of damage.…”

mentioning

confidence: 99%

Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type Alterations

Aihara

Matthis

Karns

et al. 2016

Cellular and Molecular Gastroenterology and Hepatology

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Background & Aim The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. Methods Gastric ulcers were induced in mice by serosal topical application of acetic acid. Results Gastric ulcers induced by acetic acid visually healed within 30 days. However, regenerated epithelial architecture was poor. The gene profile of regenerated tissue was abnormal, indicating increased stem/progenitor cells, deficient differentiated gastric cell types, and deranged cell homeostasis. Despite upregulation of PDX1 in the regenerated epithelium, no mature antral cell type was observed. Four months after healing, the regenerated epithelium lacks parietal cells, TFF2 and SOX9 remain upregulated deep in the gastric gland, and the Na/H exchanger 2 (a TFF2 effector in gastric healing) remains downregulated. Gastric ulcer healing was strongly delayed in TFF2 knockout mice, and re-epithelialization was accompanied with mucous metaplasia. Following H. pylori inoculum 30 days after ulceration, we observed that the gastric ulcer selectively relapses at the same site where it was originally induced. Follow up at 8 months showed that the relapsed ulcer was not healed in H. pylori infected tissues. Conclusion These findings reveal that this macroscopically regenerated epithelium has prolonged abnormal cell distribution and is differentially susceptible to subsequent damage by H. pylori.

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Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer

Cited by 23 publications

References 32 publications

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice

Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model

Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type Alterations

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