栀子石油醚有效部位的快速抗抑郁潜力与BDNF、p-eEF2的表达上调相关  

Potent rapid antidepressant effects of effective fraction of GJ-PE and up-regulation of BDNF and TrkB

作　　者：任荔[1,2] 陶伟伟[1,2] 柴毅[1,2] 李守雪 王省[1,2] 张煜萱 陈丽[1,2] 夏宝妹[1,2] 吴颢昕[1,2] 陈刚[1,2] REN Li TAO Wei-wei CHAI Yi LI Shou-xue WANG Xing ZHANG Yu-xuan CHEN Li XIA Bao-mei WU Hao-xing CHEN Gang(Center for Translational Systems and Neuroscience, School of Basic Biomedical Science Key Laboratory of Integrative Biomedicine of Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China)

机构地区：[1]南京中医药大学基础医学院转化系统生物学与神经科学研究中心,江苏南京210023 [2]南京中医药大学中医脑病重点实验室,江苏南京210023

出　　处：《中国药理学通报》2016年第9期1224-1230,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金(No 81403041);江苏省自然科学基金资助项目(No BK20151568);江苏省高校优势学科支持项目(PAPD)

摘　　要：目的筛选出栀子石油醚有效部位具有快速抗抑郁潜力并对其初始起效时间点及生物学机制进行了探讨。方法采用给药后24 h进行小鼠悬尾实验、强迫游泳实验和新奇抑制摄食实验来初步筛选具有快速抗抑郁潜力的栀子石油醚有效部位。给药30 min后进行悬尾行为实验及给药2h后进行强迫游泳实验以测试栀子石油醚有效部位起效时间。Western blot实验检测2 h及24 h小鼠海马区BDNF及p-e EF2蛋白的表达。结果单次给药GJ-PE1后2 h到24 h均能降低小鼠强迫游泳行为的不动时间,同时降低小鼠陌生环境下摄食的潜伏时间。GJ-PE3单次给药24 h后能降低小鼠陌生环境下摄食的潜伏时间。GJ-PE4给药24 h后能增加小鼠陌生环境下的摄食量。给药2 h后,GJ-PE1小鼠海马中的BDNF表达明显上调而p-e EF2表达明显下调,24 h后小鼠海马中BDNF表达明显下调而p-e EF2表达明显上调。结论栀子石油醚的4个下分部位中,GJ-PE1最具有快速抗抑郁潜力,起效时间为给药后2 h,其机制与BDNF的上调及p-e EF2的下调相关。GJ-PE3、GJ-PE4具有部分潜在快速起效抗抑郁药物的特征。GJ-PE2不具有快速抗抑郁潜力。Aim To identify whether the petroleum ether fraction of Gardenia jasminoides Ellis（ GJ-PE）could effetive exhibit a rapid antidepressant effect and also to investigate the biological mechanism. Methods Tail suspension test（ TST）,forced swimming test（ FST） and novelty suppressed-feeding（ NSF） were used to screen the rapid antidepressant potential of effective fractions of GJ-PE in KM mice at 24 h post a single administration. Tail suspension test（ TST） was also used at 30 min and forced swimming test（ FST）was used at 2 h to test the initial onset time of effective fractions of GJ-PE in KM mice. Western blot was performed to examine the expression of BDNF and p-e EF2 in hippocampus of KM mice at 2 h and 24 h. Results An acute administration of GJ-PE1 decreased the immobility time of KM mice in FST at 2 h and 24 h and decreased the latency time in NSF at 24 h. GJ-PE3 decreased the latency time in NSF at 24 h. GJ-PE4 increased the unit food consumption in NSF at 24 h. At 2h post a single GJ-PE1 treatment,the expression of BDNF was significantly up-regulated while the expression of p-e EF2 was significantly down-regulated. At 24 h post a single GJ-PE1 treatment,the expression of BDNF was significantly down-regulated while p-e EF2 expression was significantly up-regulated. Conclusion GJ-PE1 has the most significant rapid antidepressant potential among the four fractions of GJ-PE. The effective time of GJ-PE1 is 2 h after drug treatment. The mechanism of the rapid antidepressant effect of GJ-PE1 at 2 h is related to the up-regulation of BDNF and down-regulation of p-e EF2. GJ-PE3 and GJ-PE4 also have some features of rapid antidepressants. GJ-PE2doesn＇t have the rapid antidepressant potential.

关 键 词：栀子 石油醚有效部位 快速抗抑郁 BDNF p-eEF2 氯胺酮 

分 类 号：R-332[医药卫生] R284.1