ABSTRACT
Background: Abnormal expression of leptin and brain⁃derived neurotrophic factor (BDNF) is an important link in the occurrence of ulcerative colitis (UC), but the mechanism of leptin and BDNF in UC is still unclear. Aims: To explore the effect and mechanism of leptin and BDNF in DSS induced colitis in mice. Methods: Thirty⁃six male 8⁃10 weeks healthy leptin⁃deficient ob mice and leptin⁃normal expressing wild type (WT) mice were selected and randomly divided into WT experimental group, ob experimental group, WT control group and ob control group. The mice in experimental groups were given 3% DSS solution for 7 days to induce colitis model, and the mice in control group were given distilled water. After modeling, disease activity index (DAI) score, colon length, behavior and visceral sensitivity were observed. The mRNA expressions of leptin and BDNF in colon and hippocampus were detected by real⁃time fluorescent quantitative PCR, and the protein expression of BDNF in colon was detected by Western blotting. Results: Compared with corresponding control groups, DAI score, visceral sensitivity in WT experimental group and ob experimental group were significantly increased (P< 0.05), mRNA and protein expressions of BDNF in colon were significantly increased (P<0.05). Compared with WT control group, anxiety and depression⁃like behavior were found in WT experimental group, mRNA expressions of leptin, BDNF in hippocampus were significantly decreased (P<0.05). Correlation analysis showed that anxiety was positively correlated with length of colon in WT experimental group (P<0.05), and negatively correlated with DAI score (P<0.05); depression, expression of BDNF mRNA in colon were negatively correlated with length of colon (P<0.05), and positively correlated with DAI score (P<0.05); leptin in hippocampus was positively correlated with anxiety (P<0.05), while was negatively correlated with depression (P<0.05); expression of BDNF mRNA in colon was negatively correlated visceral sensitivity (P<0.05). Conclusions: Colonic BDNF secretion is associated with leptin expression, and both may be involved in the DSS⁃induced colitis in mice by mediating anxiety, depression and visceral sensitivity.
ABSTRACT
Inflammatory bowel disease (IBD) is a chronic inflammatory disease with an increasing incidence in China. Chronic inflammation is considered as an important cause of atherosclerotic cardiovascular disease (ASCVD). IBD is correlated with ASCVD. IBD and ASCVD share common pathophysiological mechanisms in epidemiology, genetics and environmental factors. Many factors related to IBD affect the occurrence and development of ASCVD. This article reviewed the common pathophysiological mechanism of the two diseases and the research progress of related treatment.
ABSTRACT
The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks. The used methods in this study were as follows: the observation of lipid droplet deposition in HepG2 cells by oil red O staining, the detection of mRNA levels of lipid metabolism-related regulators and inflammatory cytokine by RT-PCR method, the monitoring of MAPKs and PI3K/Akt pathway activation by Western blotting method. The in vitro study shows that, NACOS had no toxicity on the viability of HepG2 cells at 25-100 μg/mL and significantly reduced the deposition of lipid droplet. Also, based on both in vitro and in vivo investigation, NACOS evidently down-regulated the expression of lipid metabolism-related regulators (PGC1α, Cox5b, Mcad) and inflammatory cytokine (IL-1β) at mRNA level (P<0.05 or 0.01), and suppressed the activation of p38, ERK1/2 and Akt in HepG2 cells and lever tissues from HFD-fed mice (P<0.05 or 0.01). Based on the above, NACOS may inhibit the oxidation of liver mitochondrial fatty acid and the lipid biosynthesis, block the inflammatory responses and prevent the HepG2 cells and C57BL/6 mice from lipidemia.