Expression of Circadian Clock Genes and Their Related Genes in the Rat Colon: Studies of Feeding and Inflammatory Responses

• Main Authors: Hsiu-Ting Hsieh, 謝秀庭
• Other Authors: Kun-Ruey Shieh
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/98671358658753678319

碩士 === 慈濟大學 === 神經科學研究所 === 97 === Recent studies have shown that the circadian-clock genes present not only in the central nervous system but also in numerous peripheral organs, such as the liver, kidney and heart. The gastrointestinal tract exhibits 24-hour rhythms in many physiological functions such as gut motility, mucosal enzyme activities, mucosal transporters, and proliferation rates. While food is available only to the light-on part of a light-dark cycle in murine, circadian-clock genes expression in the liver, pancreas, and heart becomes phase-shift relative to that in animals fed ad libitum, this suggest that time feeding is an important cue in the murine to regulate circadian-clock genes and their related genes expression in the colon. Additionally, colonic disorders might be also related to circadian disruption. For example, colorectal cancer risk is increased in shift workers with presumed circadian disruption. The role of circadian-clock genes and their related genes in colonic disorders was still unclear. The main goal in this study is to investigate whether colon had daily patterns of the circadian-clock genes expression and whether these patterns were influenced by feeding and colitis. Real-time Quantitative PCR to examine the expression levels of Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, CK1ε, Dbp, Rev-erbα, Rev-erbβ, Id2, PGC1α, PGC1β, NHE3, TRPV1, NGF, BDNF, CB1 and CB2 genes in the colon of male adult Spraque-Dawley rat was used in this study. Colitis was induced by intracolonal instillation of 3% (v/v) acetic acid. The levels of inflammation was determined by histology, measurement of colonic epithelial permeability with Evans blue and myeloperoxidase activity as oxidative stress makers and inflammatory cytokines, INFα1, TNFα, IL-1β, IL-6 and IL-10, genes expression levels. We found that expression of Per1, Per2, Per3, Cry1, Cry 2, Bmal1, CK1ε, Dbp, Rev-erbα, Rev-erbβ, Id2, PGC1α, PGC1β, NHE3 and TRPV1 genes exhibited daily rhythm in the colon, but Clock, NGF, BDNF, CB1, and CB2 did not. Time feeding rest their patterns, and time feeding combined fasting not only rest these patterns but also increased their expression level. Fasting affect the expression levels of colonic circadian-clock genes and their related genes, but not the daily patterns of them. Colitis significantly increased the expression levels of circadian-clock genes and their related genes, and disrupted daily patterns of them. In contrast, these gene expression levels were restored as control while colitis was diminished or dismissed. In conclusion, circadian-clock genes may play an important role on homeostasis or stability in colon.