ABSTRACT
Activating metabolite glutamate receptor 8 (mGluR8) has anti-hyperpathia effect in central nervous system, however, studies of effects in gastrointestinal tract are rare. Visceral hypersensitivity is one of the pathogenesis factors of irritable bowel syndrome (IBS). Aims: To investigate the effect and potential mechanism of activating mGluR8 on visceral hypersensitivity in neonatal maternally separated (NMS) rats. Methods: Twenty-four male newborn SD rats were randomly divided into normal control (NC) group, NMS group and mGluR8 agonist (S)-3, 4-DCPG group (3, 10 mg/kg). Newborn rats were subjected to 3 hours daily maternal separation on postnatal day 2-14 to establish the NMS model; in (S)-3, 4-DCPG group, (S)-3, 4-DCPG (3 or 10 mg/kg) were administered 1 hour prior to the visceral sensitivity test in NMS rats. Abdominal withdrawal reflex (AWR) score and abdominal electromyography (EMG) activity were used to measure visceral sensitivity. mGluR8 mRNA and protein expressions in colon mucosa were measured by RT-PCR and Western blotting, respectively; TNF-α, IL-1β and IL-6 mRNA expressions in colon mucosa were measured by RT-PCR. The protein expression of myeloperoxidase (MPO) was measured by immunohistochemistry. Results: AWR score and EMG activity in NMS group were significantly higher than those in NC group under different colorectal distension (CRD) pressure. AWR score and EMG activity were significantly decreased in (S)-3, 4-DCPG group. mGluR8 mRNA and protein expressions in NMS group were significantly higher than those in NC group (P<0.05). Compared with NMS group, TNF-α mRNA expression was significantly decreased in 3 mg/kg (S)-3, 4-DCPG group (P<0.05), and MPO protein expression was significantly decreased in 10 mg/kg (S)-3, 4-DCPG group (P<0.05). Conclusions: Activating mGluR8 attenuates visceral hypersensitivity in NMS rats, the mechanism may be related to decrease of pro-inflammatory cytokine TNF-α.
ABSTRACT
Objective To study the correlation between vitamin D receptor (VDR) gene polymorphism and the risk of colorectal cancer.Methods Three hundred and fifty patients with colorectal cancer treated in our hospital from May 2013 to August 2016 were randomly selected as the study group,and 350 healthy subjects were recruited in this study.The genomic DNA was extracted from peripheral blood of all subjects.Twenty-nine VDR single nucleotide polymorphisms (SNPs) were selected and genotyped,and the plasma vitamin D concentration was measured.Logistic regression model was used to evaluate the odds ratio (OR) and 95％ confidence interval (CI) of colorectal cancer.Results Rs2254210,rs1540339,rs2107301,rs11168267,rs11574113,rs731236,rs3847987 and rs11574143 VDR SNPs were associated with the risk of colorectal cancer (P ＜ 0.05),and the risk of colorectal cancer was significantly higher than that of colorectal cancer (P ＜ 0.05).The SNPs of rs11574113,rs3847987 and rs11574143 were more correlated with the risk of colorectal cancer in people with higher plasma vitamin D concentrations.There was a significant difference in the proportion of patients with genotype at different levels of plasma vitamin D in the rs7968585 locus (P ＜ 0.05).Conclusion The polymorphism of vitamin D receptor gene has a certain correlation with the risk of colorectal cancer,and the detection of vitamin D gene polymorphism has a certain significance for predicting the occurrence of colorectal cancer and guiding clinical medicine.