原花青素对慢性应激模型大鼠抑郁焦虑样行为的改善作用

摘要

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.%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。