Rhubarb monomers protect intestinal mucosal barrier in sepsis via junction proteins

Wang LV¹， Cui Yun-Liang²， Zhang Zhe¹， Lin Zhao-Fen¹， Chen De-Chang¹

1.Department of Emergency and Critical Care Medicine， Changzheng Hospital， Second Military Medical University
2.Department of Critical Care Medicine， Jinan Military General Hospital

目的: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multi-organ failure. We hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.

方法: Healthy male Sprague-Dawley rats (weighing 230–250g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned into 8 groups (n=6 or 8 each group ): sham group (group A; normal saline gavage); sepsis group (group B; normal saline gavage); group C (i.p. dexamesone 0.5 mg/kg)
immediately after CLP surgery; rhubarb monomer (100mg/kg in normal saline)-treated groups: rhein (group D), emodin (group E),3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid (group F),1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose (group G), and daucosterol linoleate (group H). Animals were sacrificed after 24h. Intestinal histology,
lactulose, mannitol concentrations, ZO-1, occludin and claudin-5 transcription (PCR), translation (Western blot) and expression (immunohistochemistry) were measured.

结果: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis (group B) versus sham group (group A). Compared with group A, the pathological scores in groups B
(t=8.90, P<0.001), C (t=5.76, P<0.001),D (t=4.19, P<0.001),E (t=5.23,P<0.001), F (t=5.23,P<0.001), G (t=5.23,P<0.001), and H (t=6.28,P <0.001) were significantly decreased. Lactulose/mannitol (L/M) ratio in group B was significantly higher than in group A (t=24.00, P < 0.001); while L/M ratios in groups C (t=12.79,P< 0.001), D (t=12.07, P <0.001), E(t=14.57,P<0.001), F (t=14.56, P<0.001), G (t=11.83,P<0.001), and H (t=14.17, 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).