摘要
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OPC 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OPC 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。
OBJECTIVE To investigate the antidepressant and antianxiety effect of proanthocyanidins( OPC) in chronically stressed rats and its underlying mechanism. METHODS One method was selected from 8 different stress methods each day,and the rats were treated with OPC( 25,50 and 100 mg·kg^-1) 1 h before the stress method. The chronically stressed model was established. After 21 d stress experiment,the immobility time in force swimming test,sucrose consumption and the number of marbles buried in the marble burying test were observed respectively each day. OPC( 25,50 and 100 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-binding protein( p-CREB) in the hippocampus and frontal cortex. RESULTS Compared with the control group,the chronically stressed group showed obvious depressive-like and anxiety-like behavior,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^-1respectively,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 100 mg· kg^-1respectively,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. 18( P〈0. 05) when ig given OPC 50 and 100 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 and frontal cortex in OPC group( 50 and 100 mg·kg^-1)( P〈0.05). CONCLUSION OPC can reverse the depressive-like and anxiety-like behavior in chronically stressed r
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2014年第3期345-350,共6页
Chinese Journal of Pharmacology and Toxicology
基金
温州市科技计划项目(Y20120002)
鹿城区科技计划项目(S11101)~~
关键词
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
proanthocyanidins
chronic stress
depression
anxiety
brain derived neurotrophic fac-tor
cyclic AMP response element-binding protein