眼科新进展2024，Vol.44Issue(4)：264-269,6.DOI:10.13389/j.cnki.rao.2024.0052
SR8278改善时差所致小鼠泪腺功能紊乱的转录组学分析
Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction in-duced by jet lag in mice
摘要
Abstract
Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.关键词
时差/SR8278/泪腺/功能紊乱/小鼠Key words
jet lag/SR8278/lacrimal gland/dysfunction/mice分类
医药卫生引用本文复制引用
黄深振,李志杰,齐迪,裴晓婷,路顶立,司宏丽,黄杜鎏睿,张文潇,巴梦茹,轩书婷..SR8278改善时差所致小鼠泪腺功能紊乱的转录组学分析[J].眼科新进展,2024,44(4):264-269,6.基金项目
国家自然科学基金(编号:82101089,82171014,81770962) （编号:82101089,82171014,81770962）
河南省眼科研究所/河南省立眼科医院基础研究专项(编号:21JCZD001,23JCZD002) （编号:21JCZD001,23JCZD002）
河南省医学科技攻关计划省部共建(重点)项目(编号:SBGJ202302098) （重点）
河南省医学科学院青年医学科研人员研究项目(编号:QNYJ2023014) （编号:QNYJ2023014）
