The effect of cornus officinalis glycoside on the intestinal mucosal barrier of septic rats by regulating the NF-κB/NLRP3 pathway
10.3760/cma.j.cn431274-20231224-00713
- VernacularTitle:山茱萸新苷介导NF-κB/NLRP3通路对脓毒症大鼠肠黏膜屏障的影响
- Author:
Kaili CHEN
1
;
Ting WANG
;
Zhihao LUO
Author Information
1. 广东省中医院海南医院急救中心，海口 570203
- Keywords:
Sepsis;
Cornus officinalis glycoside;
Intestinal mucosa;
NF-κB/NLRP3 signaling pathway
- From:
Journal of Chinese Physician
2024;26(10):1488-1494
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of cornus officinalis glycoside on intestinal mucosal barrier in septic rats and its possible mechanism of action.Methods:A total of 90 Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, a dexamethasone group (10 mg/kg), a low-dose group of cornus officinalis glycoside (12.5 mg/kg), a medium dose group of cornus officinalis glycoside (25 mg/kg), and a high-dose group of cornus officinalis glycoside (50 mg/kg), with 15 rats in each group. Except for the sham surgery group, all other groups of rats were treated with cecal ligation and puncture (CLP) to prepare sepsis models. Drug intervention was administered via tail vein injection, and serum and ileal tissue were collected from rats 24 hours after surgery. Hematoxylin eosin staining (HE) was used to observe the pathological damage of the small intestinal mucosa; Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO), markers of mucosal barrier permeability, as well as the levels of small intestinal mucosal secreted immunoglobulin (sIgA) in serum; The FITC Dextran tracer method was used to detect intestinal mucosal permeability; ELISA method was used to detect the expression levels of interleukin-1 β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor -α (TNF-α) in serum; Western blot was used to detect the protein expression levels of nuclear transcription factor (NF-κB) p65, p-NF-κB p65, NOD like receptor heat protein domain associated protein 3 (NLRP3), and cysteine containing aspartic protease 1 (caspase-1) in small intestine tissue.Results:HE staining results showed that compared with the sham surgery group, the model group rats had a loss of intestinal mucosal structure, shortened villi, and infiltration of inflammatory cells; Compared with the model group, the intestinal mucosal structure of rats in the middle and high dose groups of cornus officinalis glycoside and dexamethasone group was relatively intact, with tightly arranged villi and reduced infiltration of inflammatory cells. However, the pathological improvement of intestinal mucosal structure, villi arrangement, and infiltration of inflammatory cells in rats in the low dose group of cornus officinalis glycoside was not significant. The levels of I-FABP and DAO in the serum of the model group rats were significantly higher than those in the sham operation group (all P<0.05), and the level of sIgA in the intestinal mucosa was lower than that in the sham operation group ( P<0.05). The serum levels of I-FABP and DAO in the high-dose and dexamethasone groups of cornus officinalis glycosides were lower than those in the model group (all P<0.05), and the intestinal mucosal sIgA level was higher than that in the model group ( P<0.05). However, there was no statistically significant difference in the serum levels of I-FABP, DAO, and intestinal mucosal sIgA between the low-dose cornus officinalis glycosides group and the model group (all P>0.05). The serum FITC Dextran content in the model group rats was higher than that in the sham operation group ( P<0.05); The levels of FITC Dextran in the serum of rats in the middle and high dose groups of cornus officinalis glycoside and dexamethasone group were lower than those in the model group (all P<0.05), while there was no statistically significant difference in the levels of FITC Dextran in the serum of rats in the low dose group of cornus officinalis glycoside compared with the model group ( P>0.05). The levels of IL-1 β, TNF - α, IL-6, and IL-18 in the serum of the model group rats were higher than those in the sham operation group (all P<0.05); The levels of IL-1 β, TNF-α, IL-6, and IL-18 in the serum of rats in the high-dose and dexamethasone groups of cornus officinalis glycoside were lower than those in the model group (all P<0.05), while there was no statistically significant difference in various indicators between the low-dose cornus officinalis glycoside group and the model group (all P>0.05). The protein expression levels of p-NF-κB p65/NF-κB p65, NLRP3, and caspase-1 in the small intestine tissue of the model group rats were higher than those in the sham operation group (all P<0.05); The protein expression levels of p-NF-κB p65/NF-κB p65, NLRP3, and caspase-1 in the small intestine tissues of rats in the high-dose and dexamethasone groups of cornus officinalis glycoside were lower than those in the model group ( P<0.05), while there was no statistically significant difference in the protein expression levels between the low-dose cornus officinalis glycoside group and the model group (all P>0.05). Conclusions:Cornus officinalis glycoside has a certain improvement effect on intestinal mucosal barrier dysfunction in septic rats, and its mechanism may be related to the inhibition of NF-κ B/NLRP3 signaling pathway activation.
