中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
3期
345-350
,共6页
土文珍%吴凡%严奇植%杨学志%林中%徐震%石华孟%潘建春
土文珍%吳凡%嚴奇植%楊學誌%林中%徐震%石華孟%潘建春
토문진%오범%엄기식%양학지%림중%서진%석화맹%반건춘
原花青素%慢性应激%抑郁%焦虑%脑源性神经营养因子%cAMP反应元件结合蛋白
原花青素%慢性應激%抑鬱%焦慮%腦源性神經營養因子%cAMP反應元件結閤蛋白
원화청소%만성응격%억욱%초필%뇌원성신경영양인자%cAMP반응원건결합단백
proanthocyanidins%chronic stress%depression%anxiety%brain derived neurotrophic factor%cyclic AMP response ele ment-binding protein
目的:研究原花青素(OPC)对慢性应激模型大鼠抑郁焦虑样行为的影响及可能的作用机制。方法采用8种不同的应激因素,每天1种。应激前1 h ig给予O PC 25,50和100 mg·kg -1,连续21 d。从第22天起,给予药物处理1 h后,每天检测一个行为学指标。采用强迫游泳实验测定不动时间;测定糖水偏嗜和大理石掩埋颗数;行为学测试结束后处死大鼠取组织,采用Western蛋白质印迹法测定海马和前额叶内脑源性神经营养因子(BDNF)和磷酸化cAMP反应元件结合蛋白(p-CREB)的表达。结果慢性应激组大鼠表现出明显的抑郁焦虑样行为,而给予O PC 25,50和100 mg·kg -1后在强迫游泳测试中的不动时间则分别由慢性应激组的(90.57±4.27)s 下降为(78.25±2.53)s (P<0.05),(72.12±3.21)s(P<0.05)和(60.77±3.41)s (P<0.05)。OPC 50和100 mg·kg -1组糖水消耗率则由慢性应激组的(42.80±4.92)%增加为(67.54±4.32)%(P<0.05)和(72.21±7.99)%(P<0.05),OPC 50和100 mg·kg -1组的大理石掩埋颗数由慢性应激组的1.57±0.21下降为0.63±0.26(P<0.05)和0.44±0.18(P<0.05)。OPC 25,50和100 mg·kg -1组海马内p-CREB的表达均有显著性增加(P<0.05),前额叶内p-CREB的表达亦显著性增加(P<0.05),OPC 50和100 mg·kg -1组海马及前额叶中BDNF的表达也均有增加(P<0.05)。结论 OPC可以改善由于慢性应激对大鼠造成的抑郁和焦虑样行为,其机制可能与其能够增强cAMP-CREB-BDNF信号转导通路有关。
目的:研究原花青素(OPC)對慢性應激模型大鼠抑鬱焦慮樣行為的影響及可能的作用機製。方法採用8種不同的應激因素,每天1種。應激前1 h ig給予O PC 25,50和100 mg·kg -1,連續21 d。從第22天起,給予藥物處理1 h後,每天檢測一箇行為學指標。採用彊迫遊泳實驗測定不動時間;測定糖水偏嗜和大理石掩埋顆數;行為學測試結束後處死大鼠取組織,採用Western蛋白質印跡法測定海馬和前額葉內腦源性神經營養因子(BDNF)和燐痠化cAMP反應元件結閤蛋白(p-CREB)的錶達。結果慢性應激組大鼠錶現齣明顯的抑鬱焦慮樣行為,而給予O PC 25,50和100 mg·kg -1後在彊迫遊泳測試中的不動時間則分彆由慢性應激組的(90.57±4.27)s 下降為(78.25±2.53)s (P<0.05),(72.12±3.21)s(P<0.05)和(60.77±3.41)s (P<0.05)。OPC 50和100 mg·kg -1組糖水消耗率則由慢性應激組的(42.80±4.92)%增加為(67.54±4.32)%(P<0.05)和(72.21±7.99)%(P<0.05),OPC 50和100 mg·kg -1組的大理石掩埋顆數由慢性應激組的1.57±0.21下降為0.63±0.26(P<0.05)和0.44±0.18(P<0.05)。OPC 25,50和100 mg·kg -1組海馬內p-CREB的錶達均有顯著性增加(P<0.05),前額葉內p-CREB的錶達亦顯著性增加(P<0.05),OPC 50和100 mg·kg -1組海馬及前額葉中BDNF的錶達也均有增加(P<0.05)。結論 OPC可以改善由于慢性應激對大鼠造成的抑鬱和焦慮樣行為,其機製可能與其能夠增彊cAMP-CREB-BDNF信號轉導通路有關。
목적:연구원화청소(OPC)대만성응격모형대서억욱초필양행위적영향급가능적작용궤제。방법채용8충불동적응격인소,매천1충。응격전1 h ig급여O PC 25,50화100 mg·kg -1,련속21 d。종제22천기,급여약물처리1 h후,매천검측일개행위학지표。채용강박유영실험측정불동시간;측정당수편기화대리석엄매과수;행위학측시결속후처사대서취조직,채용Western단백질인적법측정해마화전액협내뇌원성신경영양인자(BDNF)화린산화cAMP반응원건결합단백(p-CREB)적표체。결과만성응격조대서표현출명현적억욱초필양행위,이급여O PC 25,50화100 mg·kg -1후재강박유영측시중적불동시간칙분별유만성응격조적(90.57±4.27)s 하강위(78.25±2.53)s (P<0.05),(72.12±3.21)s(P<0.05)화(60.77±3.41)s (P<0.05)。OPC 50화100 mg·kg -1조당수소모솔칙유만성응격조적(42.80±4.92)%증가위(67.54±4.32)%(P<0.05)화(72.21±7.99)%(P<0.05),OPC 50화100 mg·kg -1조적대리석엄매과수유만성응격조적1.57±0.21하강위0.63±0.26(P<0.05)화0.44±0.18(P<0.05)。OPC 25,50화100 mg·kg -1조해마내p-CREB적표체균유현저성증가(P<0.05),전액협내p-CREB적표체역현저성증가(P<0.05),OPC 50화100 mg·kg -1조해마급전액협중BDNF적표체야균유증가(P<0.05)。결론 OPC가이개선유우만성응격대대서조성적억욱화초필양행위,기궤제가능여기능구증강cAMP-CREB-BDNF신호전도통로유관。
OBJECTIVE Toinvestigatetheantidepressantandantianxietyeffectofproanthocyani-dins(OPC)inchronicallystressedratsanditsunderlyingmechanism.METHODS Onemethodwas selected from 8 different stress methods each day,and the rats were treated with OPC (25,50 and 1 00 mg·kg -1 )1 h before the stress method.The chronically stressed model was established.After 21 d stress experi ment,the i mmobility ti me in force swi mming test,sucrose consu mption and the nu mber of marbles buried in the marble burying test were observed respectively each day.OPC (25,50 and 1 00 mg·kg -1 )was given 1 h before each test.In addition,Western blotting was used to analyze the expression of brain derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-bindingprotein(p-CREB)inthehippocampusandfrontalcortex.RESULTS Comparedwith the control group,the chronically stressed group showed obvious depressive-like and anxiety-like behav-ior,while the immobility time decreased from (90.57 ±4.27)s in chronically stressed group to (78.25 ± 2.53)s (P<0.05),(72.12 ±3.21 )s(P<0.05)and (60.77 ±3.41 )s (P<0.05)when ig given OPC 25,50 and 100 mg·kg -1 respectively,the ratio of sucrose preference increased from (42.80 ±4.92)%to (67.54 ±4.32)%(P<0.05)and (72.21 ±7.99)%(P<0.05)when ig given OPC 50 and 1 00 mg· kg -1 respectively,the number of buried marbles decreased from 1 .57 ±0.21 in chronically stressed group to 0.63 ±0.26 (P<0.05)and 0.44 ±0.1 8 (P<0.05)when ig given OPC 50 and 1 00 mg·kg -1 respectively.The expression of p-CREB in the hippocampus and frontal cortex distinctively increased in OPC group (25,50 and 100 mg·kg -1 )(P<0.05),so did the expression of BDNF in the hippocampus andfrontalcortexinOPCgroup(50and100mg·kg-1)(P<0.05).CONCLUSION OPCcanreverse the depressive-like and anxiety-like behavior in chronically stressed rats,which may be related to the cAMP-CREB-BDNF signal transduction cascades.