[1]黄深振,齐迪,裴晓婷,等.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.[doi:10.13389/j.cnki.rao.2024.0052]
　HUANG Shenzhen,QI Di,PEI Xiaoting,et al.Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction induced by jet lag in mice[J].Recent Advances in Ophthalmology,2024,44(4):264-269.[doi:10.13389/j.cnki.rao.2024.0052]
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SR8278改善时差所致小鼠泪腺功能紊乱的转录组学分析/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
44卷
期数:
2024年4期
页码:
264-269
栏目:
实验研究
出版日期:
2024-04-05

文章信息/Info

Title:
Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction induced by jet lag in mice
作者:
黄深振; 齐迪; 裴晓婷; 路顶立; 司宏丽; 黄杜鎏睿; 张文潇; 巴梦茹; 轩书婷; 李志杰
450003　河南省郑州市，郑州大学人民医院，河南省人民医院，河南大学人民医院，河南省立眼科医院，河南省眼科研究所
Author(s):
HUANG Shenzhen; QI Di; PEI Xiaoting; LU Dingli; SI Hongli; HUANG Duliurui; ZHANG Wenxiao; BA Mengru; XUAN Shuting; LI Zhijie
Henan Eye Institute,Henan Eye Hospital,People’s Hospital of Henan University,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,Zhengzhou 450003,Henan Province，China
关键词:
时差; SR8278; 泪腺; 功能紊乱; 小鼠
Keywords:
jet lag;  SR8278;  lacrimal gland;  dysfunction;  mice
分类号:
R777.2
DOI:
10.13389/j.cnki.rao.2024.0052
文献标志码:
A
摘要:
目的　探讨核受体亚家族1 D组成员1（NR1D1）合成拮抗剂 SR8278 在改善时差诱导的小鼠眶外泪腺结构和功能损伤方面的作用及其机制。
方法　36只健康的8~10周龄野生型C57BL/6J小鼠在12 h光照/12 h黑暗循环的昼夜节律箱内适应2周后随机分为3组：正常组（12 h光照/12 h黑暗循环的昼夜节律箱饲养）、时差组（8 h前移的12 h光照/12 h黑暗循环的昼夜节律箱饲养）及时差+SR8278组（8 h前移的12 h光照/12 h黑暗循环的昼夜节律箱饲养，并给予25 mg·kg-1的SR8278干预），每组12只，共干预5 d。干预结束后，收集各组小鼠的活动度和核心体温，记录小鼠的泪液分泌量，并对泪腺组织进行称重和泪腺细胞大小测量。采用免疫组织化学方法对小鼠眶外泪腺进行组织学评估。提取泪腺RNA进行包含NR1D1的高通量RNA-Seq分析，并对获得的转录组数据进行KEGG和GO功能富集分析。
结果　与正常组相比，时差组小鼠白天活动度较高，夜间活动度较低，白天核心体温较高，夜间核心体温较低，差异均有统计学意义（均为P<0.05）。与时差组相比，时差+SR8278组小鼠白天活动度较低，夜间活动度较高，白天核心体温较低，夜间核心体温较高，差异均有统计学意义（均为P<0.05）。与正常组相比，时差组小鼠泪腺重量及泪液分泌量降低，泪腺细胞增大，差异均有统计学意义（均为P<0.05）；与时差组相比，时差+SR8278组小鼠泪腺重量及泪液分泌量增加，泪腺细胞减小，差异均有统计学意义（均为P<0.05）。与正常组相比，时差组小鼠夜晚泪腺中NR1D1表达量较高；与时差组相比，时差+SR8278组小鼠夜晚泪腺中NR1D1表达量较低，差异均有统计学意义（均为P<0.05）。生物信息学分析显示，时差组和时差+SR8278组共有947个显著性差异基因，其中显著性上调基因43个，显著性下调基因904个，信号通路差异最大的为Notch 信号通路。
结论　SR8278通过靶向抑制NR1D1，有效增强了时差小鼠的泪液分泌功能，其过程可能是通过Notch信号通路完成的。
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 divided 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 extraorbital 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.
Results　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 activity, lower daytime core body temperature, and higher nighttime core body temperature, with statistically significant differences (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 NR1D1 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.

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备注/Memo

备注/Memo:
国家自然科学基金（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）；河南省医学科技攻关计划省部共建（重点）项目（编号：SBGJ202302098）；河南省医学科学院青年医学科研人员研究项目（编号：QNYJ2023014）
更新日期/Last Update: 2024-04-05