中国比较医学杂志2026，Vol.36Issue(4)：35-51,17.DOI:10.3969/j.issn.1671-7856.2026.04.004
基于营卫理论探讨昼夜节律对失眠模型小鼠核心生物钟基因的影响
Effects of circadian rhythm on core circadian clock genes in insomnia model mice based on Ying-Wei theory
摘要
Abstract
Objective To investigate the pathological role of circadian rhythm disorders in insomnia by destroying the molecular oscillation mechanism of hypothalamus-amygdala core circadian clock genes,and to provides dynamic molecular evidence for the Ying-Wei theory of insomnia circadian clock gene disorder.Methods 104 six-week-old female ICR mice were divided randomly into normal and PCPA groups(n=52 per group).Mice in PCPA group received intraperitoneal injections of PCPA for 3 days and normal mice received equivalent volumes of saline.Behavioral tests were conducted to evaluate sleep latency,total sleep duration,and anxiety-depression-like behaviors.Nuclear translocation of period circadian regulator 1(PER 1)and cryptochrome circadian regulator 1(CRY 1)in the hypothalamus and amygdala were detected by immunofluorescence at different time point(6:00,12:00,18:00,24:00),and mRNA and relative protein expression levels of circadian clock genes were detected by quantitative reverse transcription-polymerase chain reaction and Western blot,respectively.Results Compared with normal group,mice in PCPA group exhibited prolonged sleep latency,reduced sleep duration(P＜0.01),decreased sucrose preference(P＜0.01),increased grooming frequency,and extended central exploration distance in the open field test(P＜0.01).Compared with normal group,mRNA and protein levels of core clock genes(PER1,CRY 1,CLOCK,and BMAL1)differed at different time points,with inconsistent expression patterns between the hypothalamus and amygdala.Peak nuclear co-localization of PER1 and CRY1 proteins in the hypothalamus was advanced by 4～6 hours in PCPA group,while their nuclear co-localization peaks in the amygdala were phase-shifted by approximately 12 hours compared with normal group.Conclusions Circadian rhythm disturbance caused by an imbalance of Camp and Defense may be related to the circadian rhythm oscillation and phase shift of core clock genes in different brain regions,potentially manifested as phase shifts of PER1 and CRY1 into the nucleus to form complexes.关键词
失眠/营卫/昼夜节律/核心生物钟基因/下丘脑/杏仁核Key words
insomnia/Ying-Wei/circadian rhythm/core circadian clock genes/hypothalamus/amygdala分类
医药卫生引用本文复制引用
杨晶,何宗卿,刘迟晓,郑育新,王小燕,刘飞祥,赵敏..基于营卫理论探讨昼夜节律对失眠模型小鼠核心生物钟基因的影响[J].中国比较医学杂志,2026,36(4):35-51,17.基金项目
河南省联合基金项目(232301420022) （232301420022）
国家中医药传承专项(2022CCCX008) （2022CCCX008）
