β-细辛醚改变抑郁模型大鼠行为及对海马MEK-ERK级联通路的影响

Effect of Beta-asarone on Behavior and Expression of Protein MEK and ERK in Hippocampus in Rat Model of Depression

目的：探讨β-细辛醚对改善抑郁模型大鼠行为及调节大鼠海马组织中丝裂原细胞外激酶-细胞外信号调节蛋白激酶（MEK-ERK）级联通路的作用.方法：2～3月龄SD大鼠80只,分为4组（对照组、模型组、氟西汀组和β-细辛醚组）,每组20只.孤养并给予慢性轻度不可预见性刺激.于模型复制成功后第2天开始,分别给予氟西汀组和β-细辛醚组1次/d灌胃,给药剂量分别为氟西汀1.2 mg· kg-1,β-细辛醚25 mg· kg-1.于实验第1,7,14,21天,对每组大鼠进行体重测量、行为学分值评定、糖水消耗量测定.采用RT-PCR法对海马组织中MEK,ERK mRNA行定量分析.免疫组织化学法检测MEK,p-ERK蛋白表达水平.结果：与正常组比较,模型组大鼠随着造模天数增加而表现体重下降,第14天开始,体重下降明显,差异有统计学意义（P＜0.05）;Open-field-test水平、垂直运动得分与糖水偏爱度显著降低,第7天开始表现明显差异（P＜0.01）;海马组织中MEK,ERK基因水平显著降低（P ＜0.01）;MEK,p-ERK蛋白表达降低（P＜0.05）.与模型组比较,β-细辛醚组大鼠行为学评定结果改善,第14,21天体重增加差异显著（P＜0.05）;Open-field-test运动评分于14d开始升高,差异具有明显统计学意义（P＜0.01）;糖水偏爱度升高;海马组织中MEK,ERK mRNA水平上调（P＜0.01）,MEK,p-ERK蛋白表达增强,差异具有统计学意义（P＜0.05）.效果与氟西汀组相近.结论：β-细辛醚可有效缓解大鼠抑郁症状,其机制可能与增加大鼠海马组织中的MEK,p-ERK蛋白表达有关.

Objective：To investigate the effect of beta-asarone on the behaviors and the expressions of mitogen extracellular kinaes （MEK） and extra cellular signal-regulated protein kinase （ERK） in the hippocampus of depression model rats.Method：Eighty adult Sprague-Dawley rates were divided into 4 groups randomly：the normal control group; the model group; the fluoxetine control group; the β-asarone group,20 in each one.Solitary and chronic mild unpredictability were used to stimulation on each one except the normal group.On the second day of a successful model,the fluoxetine and the β-asarone group were given corresponding drugs once a day bygastrogavage for21 days （1.2 mg·kg-1·d-1 to the fluoxetine control group,25 mg·kg-1·d-1 to theβ-asarone group）.At l,7,14,21 days,weight was measured,Open-field-test and sucrose consumption volume were detected,Real-time PCR was used for quantitative analysis of MEK and ERK mRNA.The protein expression of MEK and p-ERK in the hippocampus were tested by immunohistochemical staining method.Result：Compared with the normal group,the weight of the rats in the model group was decreased,on the 14th day,the rats lose weight obviously （P ＜ 0.05）.The scores of Open-field-test and sugar water preference were reduced significantly since the 7th day of the experiment （P ＜0.01）.The level of MEK,ERK mRNA were decreased （P ＜0.01）,and the protein expressions of MEK,p-ERK were declined （P ＜ 0.05）.Compared with the model group,the scores of β-asarone group in the Open-field-test and sucrose consumption volume were improved.The changes of rats＇weight was found on the 14th day and 21th （P ＜ 0.05）.The scores of Open-field-test increased until 14th day （P ＜ 0.01）.The levels of MEK and ERK mRNA were Up-regulated （P ＜ 0.01）,the protein expressions of MEK and p-ERK were increased （P ＜ 0.05） in the hippocampus.Similar effects were observed in fluoxetin group.Conclusion：Beta-asarone could alleviate the symptoms of depression in rats effectively,its mechanism might be related to increasing the protein expression of MEK and p-ERK in the rat hippocampus.