摘要
目的:研究加味四逆散分时给药对应激性抑郁症大鼠下丘脑视交叉上核生物钟基因Per、Cry的表达及其昼夜节律的影响。方法:采用慢性不可预计轻度应激建立应激性抑郁症大鼠模型,采用RT-PCR法及余弦节律分析法观察分析抑郁症大鼠下丘脑视交叉上核Per、Cry的表达及其昼夜节律的变化。结果:慢性不可预计轻度应激使大鼠Per1、Per2、Per3、Cry2在大多数时间点(至少4个时间点)表达增强。应激性抑郁症大鼠下丘脑视交叉上核中Per12-△△Ct的中值、谷值上升,振幅增大,时相提前;Per22-△△Ct的中值、峰值上升,振幅增大,时相延后;Per32-△△Ct的中值下降、峰值上升,振幅无变化,时相延后;Cry12-△△Ct的中值、峰值、谷值下降,振幅无变化,时相延后;Cry22-△△Ct的中值、峰值上升,振幅无变化,时相提前。加味四逆散卯时给药(16.9g/kg)对Per2、Per3、Cry2表达增强以及Per2振幅增大具有明显的抑制作用;对Cry2、Per2、Per32-△△Ct的中值、谷值和峰值紊乱以及Cry1、Per3峰值时间和谷值时间的紊乱具有明显的调节作用。加味四逆散酉时给药(16.9g/kg)对Per2、Per3、Cry2表达增强以及Per1振幅增大具有明显的抑制作用;对Per2、Per32-△△Ct的中值、谷值和峰值紊乱以及Cry1、Per3峰值时间和谷值时间的紊乱具有明显的调节作用。结论:加味四逆散卯时和酉时给药主要是通过调节SCN中Per、Cry有关时间点的含量和改变其时间节律达到抗抑郁效应。
Objective：To study the effects of timeshare administration of Jiaweisinisan（JWSNS） on expression and circadian rhythm changes of Per and Cry in hypothalamus suprachiasmatic nuclei of rats with stressed depression. Methods：Chronic Unpredictable mild stress （CUMS）was used to establish the rat model of stressed depression. RT-PCR and cosine rhythm analysis was adopted to observe and analyze the expression and changes of circadian rhythms of Per and Cry in hypothalamus supraehiasmatic nuclei（SCN）. Results：CUMS enhanced the expression of Perl, Per2, Per3 and Cry2 at most of the time points（ P 〈 0.05 or P 〈 0.01 ）. In rats with stressed depression, there were increased median, valley values and amplitude, advanced phase of Perl＇s^△△Ct（ P 〈 0.05 or P 〈 0.01 ） ; increased median, peak values and amplitude, post- poned phase of Per2＇ss^△△Ct（ P 〈0.01 ） ;decreased median values, increased peak values and postponed phase of Per3＇s^△△Ct（ P 〈0.05 or P 〈 0.01 ） ; decreased median, peak, valley values and postponed phase of Cryl2s^△△Ct （ p 〈 0.05 or P 〈 0.01 ） ; increased median, peak values and advanced phase of Cry22s^△△Ct（ P 〈0.05 or P 〈0.01 ）. Administration of JWSNS（16.9g/kg） at 7：30 could inhibit the increased expression of Per2, Per3, Cry2 and Per2＇s amplitude（ P 〈 0.05 or P 〈 0.01 ）, and could regulate the disorder of median, peak and valley values of Cry2, Per2, Per32s^△△Ct, and peak, valley times of Cryl and per3 （ P 〈 0.05 or P 〈 0.01 ）. Administration of JWSNS （16.9g/kg） at 17 ： 30 could inhibit the increased expression of Per2, Per3, Cry2 and Perl＇s amplitude（ P 〈 0.05 or P 〈 0.01 ）, and could regulate the disorder of median, valley values of Per2, Per32s^△△Ct and peak, valley times of Cryland Per3（P 〈0.05 or P 〈0.01）. Conclusion：Administration of JWSNS at 7：30 and 17：30 achieve anti-depressant effects mainly by regulating the expression and circadian rhythm of Per and Cry in hypothalamus SCN at relevant time points.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2014年第1期92-98,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金资助项目(NO.30873389)
关键词
加味四逆散
应激
抑郁症
视交叉上核
生物钟基因
生物节律
Jiaweisinisan （加味四逆散）
stress
depression
supraehiasmatic nuclei
circadian clock genes
circadian rhythm
