scholarly journals Carbon Monoxide Releasing Molecule-2 Protects Intestinal Mucosal Barrier Function of Rat Undergoing Cardiopulmonary Resuscitation via Attenuation of TNF-α/NF-κB Signaling

Author(s):  
Qingsheng Niu ◽  
Fang Liu ◽  
Jun Zhang ◽  
Xiaojun Yang ◽  
Xiaohong Wang

Abstract The unique features of post–cardiac arrest pathophysiology are often superimposed on the disease or injury, causing the cardiac arrest, as well as underlying comorbidities. Exogenous carbon monoxide (CO) was reported to reduce ischemia-reperfusion injury (IRI). This study aimed to assess the effects of CO releasing molecule-2 (CORM-2) on intestinal mucosal barrier function after cardiopulmonary resuscitation (CPR) in rats. For this purpose, we established a rat model of asphyxiation-induced cardiac arrest and resuscitation to study intestinal IRI, and measured the serum level of intestinal fatty-acid binding protein (I-FABP). The expression levels of claudin-3, occludin, ZO-1, tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and nuclear factor kappa B (NF-κB) p65 were detected by Western blotting. CORM-2 up-regulated the expression levels of tight junction proteins (claudin-3, occludin, and ZO-1) in intestinal mucosa, leading to the reduction of the permeability of intestinal mucosa and reduced the release of proinflammatory cytokines. Besides, the CORM-2 exhibited anti-inflammatory effects by regulating the TNF-α/NF-κB pathway. In conclusion, CORM-2 treatment is clinically significant, preventing intestinal mucosal damage as a result of IRI during CPR.

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Changfeng Shao ◽  
Jiaqin Chen ◽  
Wei Chen ◽  
Qi Peng ◽  
Di Li ◽  
...  

Objective To study the effect of aerobic exercise on the damage of intestinal mucosal barrier function caused by obstructive jaundice(OJ)and to explore its mechanism of action. Methods  50 male KM mice were randomly divided into 5 groups: sham operation group (S), model group (M), exercise group (TM), DL-Propargylglycine + exercise (PT) group and sodium hydrosulfide + exercise (NT) group.In addition to the S group which are in the common bile duct to the abdominal wall hanging 48 hours to build mouse obstructive jaundice model. In the PT group, PAG (40 mg/kg) was intraperitoneally injected 7 days after surgery; NaHS (50 μmol/kg) was intraperitoneally injected in the NT group 7 days after surgery; TM group, NT group and PT group were graded at 0%, and the speed was 10m/min no weight training (30min/day).After 6 weeks, HE staining was used to observe the morphological changes of the intestinal mucosa.Biochemical analysis was used to detect the concentration of hydrogen sulfide (H2S) in blood and ileum, and total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) Liver function, diamine oxidase (DAO), D-lactic acid intestinal barrier function biochemical index; qRT-PCR and immunohistochemical staining were used to observe the expression changes of H2S-mediated related channel mRNA and protein(HMGB1, TLR4 and NF-Kbp6)in intestinal tissues. Results HE staining showed that the intestinal mucosa of group M was atrophied and the villus was broken.Compared with M group, the intestinal mucosa arrangement in TM group was relatively regular. Compared with TM group, intestinal mucosa atrophy in PT group, fluff hair loss, sparseness and disorder, partial mucosa The layer was separated from the lamina propria and the gland was severely damaged. The intestinal mucosa of the NT group was relatively regular, and the changes of intestinal mucosa atrophy were restored. Serum test results showed that H2S levels were higher in the TM group than in the M group; compared with the TM group, the PT group decreased and the NT group increased. DAO level: The TM group was lower than the M group; compared with the TM group, the PT group was elevated and the NT group was decreased.  Changes in serum D-lactic acid levels were similar to DAO. The results of qRT-PCR and immunohistochemical staining showed that the expressions of HMGB1, TLR4 and NF-Kbp6 mRNA and protein in the intestinal tissues of mice in TM group were significantly lower than those in M group and PT group, and the mRNA and protein expression levels in NT group were the lowest. Conclusions Aerobic exercise inhibits the HMGB1 / TLR4 / NF-κB signaling pathway through the H2S / CSE system, thereby exerting a protective effect on the intestinal mucosal barrier.


2020 ◽  
Vol 321 ◽  
pp. 73-82 ◽  
Author(s):  
Simin Shen ◽  
Jingjiao Zhao ◽  
Yicong Dai ◽  
Fengrong Chen ◽  
Zunyue Zhang ◽  
...  

2019 ◽  
Vol 20 (22) ◽  
pp. 5751 ◽  
Author(s):  
Jia Wang ◽  
Cuili Zhang ◽  
Chunmei Guo ◽  
Xinli Li

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.


2019 ◽  
Vol 20 (11) ◽  
pp. 2777 ◽  
Author(s):  
Zhihua Ren ◽  
Chaoyue Guo ◽  
Shumin Yu ◽  
Ling Zhu ◽  
Ya Wang ◽  
...  

Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms.


2018 ◽  
Vol 22 (6) ◽  
pp. 731-738 ◽  
Author(s):  
Weiying Ren ◽  
Jiayu Wu ◽  
Li Li ◽  
Y. Lu ◽  
Y. Shao ◽  
...  

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