中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
The Chinese Journal of Clinical Pharmacology
2015年
15期
1539-1542
,共4页
徐德峰%宓为峰%张素贞%李玲芝%张鸿燕
徐德峰%宓為峰%張素貞%李玲芝%張鴻燕
서덕봉%복위봉%장소정%리령지%장홍연
巴戟天寡糖%抑郁动物模型%脑源性神经营养因子%糖原合成酶激酶3β%突触蛋白
巴戟天寡糖%抑鬱動物模型%腦源性神經營養因子%糖原閤成酶激酶3β%突觸蛋白
파극천과당%억욱동물모형%뇌원성신경영양인자%당원합성매격매3β%돌촉단백
morinda officinalis how oligosaccharides%depression animal model%brain derived neurotrophic factor%GSK-3β%synapsins
目的:探讨巴戟天寡糖抗抑郁作用及可能机制。方法雄性Sprague-Dawley( SD)大鼠随机分为6组:正常组,模型组,巴戟天寡糖高、中、低剂量实验组(50,25,12.5 mg· kg-1· d-1),氟西汀组(10 mg· kg-1· d-1)。除正常组外,其余用慢性不可预见性应激法建立抑郁模型后随机分组,氟西汀组以及巴戟天寡糖各剂量实验组连续灌胃给药14 d,每天1次。用糖水偏爱测试和强迫游泳测试检测大鼠的行为变化。大鼠末次给药24 h后处死,分离海马组织,冰冻保存。蛋白免疫印迹法检测高剂量实验组对大鼠海马脑区脑源性神经营养因子( BDNF)、糖原合成酶激酶3β( GSK-3β)及突触蛋白包括谷氨酸受体亚单位-1(GluR1)、突触后致密物-95(PSD95)、突触蛋白-1(Synapsin 1)表达水平的影响。结果与模型组相比,巴戟天寡糖高、中剂量实验组及氟西汀组糖水偏爱值显著增加(P<0.05,P<0.01,P<0.01),高剂量实验组及氟西汀组强迫游泳不动时间显著缩短( P<0.01);慢性应激后,大鼠海马脑区BDNF、p-GSK-3β及GluR1、PSD95、Synapsin 1显著下降(P<0.01,P<0.05,P<0.05),高剂量实验组(50 mg · kg-1· d-1)能够显著增加大鼠海马脑区 BDNF ( P <0.05)、p-GSK-3β(P <0.01)及 GluR1、PSD95、Synapsin 1(P<0.05)的表达,而对GSK-3β蛋白总量的表达没有明显影响。结论巴戟天寡糖能够拮抗慢性应激所引起的抑郁样行为,其作用机制可能是通过影响神经营养因子通路,调节突触可塑性实现的。
目的:探討巴戟天寡糖抗抑鬱作用及可能機製。方法雄性Sprague-Dawley( SD)大鼠隨機分為6組:正常組,模型組,巴戟天寡糖高、中、低劑量實驗組(50,25,12.5 mg· kg-1· d-1),氟西汀組(10 mg· kg-1· d-1)。除正常組外,其餘用慢性不可預見性應激法建立抑鬱模型後隨機分組,氟西汀組以及巴戟天寡糖各劑量實驗組連續灌胃給藥14 d,每天1次。用糖水偏愛測試和彊迫遊泳測試檢測大鼠的行為變化。大鼠末次給藥24 h後處死,分離海馬組織,冰凍保存。蛋白免疫印跡法檢測高劑量實驗組對大鼠海馬腦區腦源性神經營養因子( BDNF)、糖原閤成酶激酶3β( GSK-3β)及突觸蛋白包括穀氨痠受體亞單位-1(GluR1)、突觸後緻密物-95(PSD95)、突觸蛋白-1(Synapsin 1)錶達水平的影響。結果與模型組相比,巴戟天寡糖高、中劑量實驗組及氟西汀組糖水偏愛值顯著增加(P<0.05,P<0.01,P<0.01),高劑量實驗組及氟西汀組彊迫遊泳不動時間顯著縮短( P<0.01);慢性應激後,大鼠海馬腦區BDNF、p-GSK-3β及GluR1、PSD95、Synapsin 1顯著下降(P<0.01,P<0.05,P<0.05),高劑量實驗組(50 mg · kg-1· d-1)能夠顯著增加大鼠海馬腦區 BDNF ( P <0.05)、p-GSK-3β(P <0.01)及 GluR1、PSD95、Synapsin 1(P<0.05)的錶達,而對GSK-3β蛋白總量的錶達沒有明顯影響。結論巴戟天寡糖能夠拮抗慢性應激所引起的抑鬱樣行為,其作用機製可能是通過影響神經營養因子通路,調節突觸可塑性實現的。
목적:탐토파극천과당항억욱작용급가능궤제。방법웅성Sprague-Dawley( SD)대서수궤분위6조:정상조,모형조,파극천과당고、중、저제량실험조(50,25,12.5 mg· kg-1· d-1),불서정조(10 mg· kg-1· d-1)。제정상조외,기여용만성불가예견성응격법건립억욱모형후수궤분조,불서정조이급파극천과당각제량실험조련속관위급약14 d,매천1차。용당수편애측시화강박유영측시검측대서적행위변화。대서말차급약24 h후처사,분리해마조직,빙동보존。단백면역인적법검측고제량실험조대대서해마뇌구뇌원성신경영양인자( BDNF)、당원합성매격매3β( GSK-3β)급돌촉단백포괄곡안산수체아단위-1(GluR1)、돌촉후치밀물-95(PSD95)、돌촉단백-1(Synapsin 1)표체수평적영향。결과여모형조상비,파극천과당고、중제량실험조급불서정조당수편애치현저증가(P<0.05,P<0.01,P<0.01),고제량실험조급불서정조강박유영불동시간현저축단( P<0.01);만성응격후,대서해마뇌구BDNF、p-GSK-3β급GluR1、PSD95、Synapsin 1현저하강(P<0.01,P<0.05,P<0.05),고제량실험조(50 mg · kg-1· d-1)능구현저증가대서해마뇌구 BDNF ( P <0.05)、p-GSK-3β(P <0.01)급 GluR1、PSD95、Synapsin 1(P<0.05)적표체,이대GSK-3β단백총량적표체몰유명현영향。결론파극천과당능구길항만성응격소인기적억욱양행위,기작용궤제가능시통과영향신경영양인자통로,조절돌촉가소성실현적。
Objective To investigate the antidepressant effect of morin-da officinalis oligosaccharides ( MOs ) and its possible mechanism. Methods Male Sprague-Dawley ( SD) rats were randomly divided into 6 groups:normal group,model group,high,moderate and low MOs dose groups ( 50, 25 and 12.5 mg · kg -1 · d-1 ) and fluoxetine group (10 mg· kg-1 · d-1 ) .Except the normal group, the rats in all other groups were given chronic unpredictable stress ( CUS ) to build the depression animal models.The fluoxetine group and the MOs groups were orally administrated once a day for 14 days.The behavioral status of rats was evluated by forced swimming test ( FST) and sucrose preference test ( SPT) .All the rats were executed 24 h after the last administration, the hippocampal tissue separated and cryopreserved for standby.The protein expression of BDNF、GSK-3βand synapsins(GluR1、PSD95、Synapsin 1) in the hippocampus of rats were tested by Western-blot.Results After 14 d of daily administration of MOs(25,50 mg· kg-1· d-1) and fluoxetine(10 mg· kg -1· d -1), sucrose preference sig-nificantly increased in stressed rats ( P <0.05 , P <0.01 , P <0.01 respectively ).Chronic administration of MOs (50 mg· kg -1· d-1) and fluoxetine (10 mg· kg -1· d-1) (P<0.01)decreased the immobility time significantly.In the hippocampus, the content of BDNF ( P <0.01 )、p -GSK -3β( P <0.05 ) and GluR1、PSD95、Synapsin 1 ( P<0.05) protein expression levels of model group were significantly lower than normal group.Chronic administration of MOs(50 mg· kg-1· d-1) increased the protein levels of BDNF(P<0.05)、p-GSK-3β(P<0.01) and GluR1、PSD95、Synapsin 1 ( P <0.05 ) , but no significant differences were measured in the protein levels of the totle GSK-3β.Conclusion MOs has a prominent therapeutic effect on mice model of chronic stress-induced depression and the underlying mechanisms could involve regulating BDNF signaling pathway and enhancing synaptic plasticity.