The association between disruption of the circadian rhythm and aggravation of colitis in mice  

作　　者：Yi-Dong Chen Rui-Feng Zhao Gen Zheng Fang-Mei Ling Jun-Rong Li Ming-Yang Xu Di Guo Qiu-Lei Zhang Shuang Li Liang-Ru Zhu 

机构地区：[1]Division of Gastroenterology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,P.R.China

出　　处：《Gastroenterology Report》2022年第1期395-404,共10页胃肠病学报道（英文）

基　　金：supported by National Key R&D Program of China[No.2018YFC0114600];National Natural Science Foundation of China[No.82170547,No.81873558].

摘　　要：Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation.The circadian rhythmcontrols cell proliferation and energy metabolism.However,the role of circadian genes in inflammatory bowel disease is largely unknown.The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism.Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days,whereas those in the control group were not.Subsequently,half of the mice in the control and jet-lagged groups were given dextran sodium sulfate(DSS)to induce colitis.Mice in each group were euthanized at zeitgeber time(ZT)0,ZT4,ZT8,ZT12,ZT16,and ZT20.To investigate the effects of jet lag on the mice,colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes(Bmal1,Clock,Per1,Per2,Cry1,Cry2,and Nr1d1).We analysed the mitochondrial morphology,adenosine triphosphate(ATP)levels,and the expression of dynamin-related protein 1(Drp1)and ser637-phosphorylated(p)-Drp1,which are closely related to ATP production.We further investigated the effect of PER2 knockdown in the colon epithelial cells(CCD 841 CoN)by measuring ATP and cell proliferation levels.Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice,altered the mitochondrial morphology of the colon specimens,decreased the expression of p-Drp1,reduced ATP production,and exacerbated inflammatory responses in mice with DSS-induced colitis.Additionally,silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation.Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.

关 键 词：circadian rhythm mitochondrial energy metabolism PER2 COLITIS inflammatory bowel disease 

分 类 号：R574.62[医药卫生—消化系统]