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Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins
Lyu Wang1, Yun-Liang Cui2, Zhe Zhang1
1Department of Emergency and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Background:
Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.
Methods:
Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured.
Results:
Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05).
Conclusion:
Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.
Insights
Rhubarb monomers protect the gut mucosal barrier in sepsis by enhancing junction proteins. This study found that rhubarb compounds improved intestinal integrity and reduced damage in a rat model of sepsis.
Area of Science:
- Gastroenterology
- Pharmacology
- Sepsis Research
Background:
- Intestinal barrier dysfunction is a critical factor in sepsis-induced multiorgan failure.
- Bacterial translocation across a compromised gut barrier contributes to systemic inflammation and organ damage.
Purpose of the Study:
- To investigate the protective effects of rhubarb monomers on the intestinal mucosal barrier in a sepsis model.
- To determine if rhubarb monomers can restore the integrity of tight junction proteins.
Main Methods:
- Cecal ligation and perforation (CLP) was used to induce sepsis in Sprague-Dawley rats.
- Rats were treated with specific rhubarb monomers (rhein, emodin, etc.) or dexamethasone.
- Intestinal histology, permeability (lactulose/mannitol ratio), and tight junction protein expression (ZO-1, occludin, claudin-5) were assessed.
Main Results:
- Sepsis induced significant intestinal mucosal damage and increased gut permeability.
- Rhubarb monomer treatment significantly reduced pathological scores and the lactulose/mannitol ratio compared to the sepsis group.
- Treatment with rhubarb monomers upregulated the transcription, translation, and expression of tight junction proteins ZO-1, occludin, and claudin-5.
Conclusions:
- Rhubarb monomers demonstrate significant protective effects against sepsis-induced intestinal mucosal damage.
- These protective effects are mediated by the enhancement of key tight junction proteins.
- Rhubarb monomers hold potential as therapeutic agents for managing intestinal barrier dysfunction in sepsis.
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