基于β-catenin介导金郁欢抗抑郁的初步研究

Antidepressant Mechanism of Jinyuhuan Meditated byβ-Catenin

目的:探讨金郁欢对抑郁小鼠行为的调节作用。方法:将60只ICR小鼠随机分为5组,control组、model组、JYH-L组、JYH-H组、fluoxetine组,每组12只。采用CMUS方法造模。利用旷场实验进行行为学研究,Nissl染色观察海马神经元形态总面积,免疫组织化学法和Western Blot法检测β-catenin蛋白水平,实时定量PCR检测β-catenin mRNA表达水平。结果:行为学旷场实验结果显示,各组小鼠水平移动得分差异无统计学意义(P>0.05);与control组比较,JYH-H组、fluoxetine组直立得分显著增加(P<0.01)。Nissl染色结果显示,与control组比较,model组海马区尼氏小体总面积显著降低(P<0.01);与model组比较,JYH-L组、JYH-H组尼氏小体总面积明显增加(P<0.05),fluoxetine组尼氏小体总面积明显增高(P<0.01)。免疫组织化学和Western Blot法检测结果显示,与control组比较,model组β-catenin蛋白表达量明显下降(P<0.01),与model组相比,JYH-L组、JYH-H组β-catenin蛋白表达显著升高(P<0.05),fluoxetine组β-catenin蛋白表达量亦升高(P<0.01)。实时定量PCR检测结果显示,与control组相比,model组β-catenin mRNA表达量明显下降(P<0.01);与model组相比,JYH-L组、JYH-H组β-catenin mRNA表达量明显升高(P<0.05),fluoxetine组β-catenin mRNA表达量明显升高(P<0.01)。结论:金郁欢能有效改善抑郁症模型小鼠的抑郁样行为,这种改善作用可能通过提高β-catenin表达实现。

Objective:To study the effects of Jinyuhuan(JYH)on depression-like behavior in depressed mice.Methods:60 ICR mice were randomly divided into the control group,the model group,the JYH-L group(low-dose),the JYH-H group(high-dose)and the Fluoxetine group,with 12 mice in each group.CMUS method was used to build the depression model.Open field test was used for behavioral tests.Nissl staining was used to observe the morphology of neurons.β-caternin protein level was detected by immunohistochemistry method and Western Blot method.The mRNA expression ofβ-catenin was detected by RT-PCR.Results:In terms of the behavioral research of open field test,there was no statistical difference in the horizontal movement scores among the groups(P>0.05).Compared with that in the control group,the vertical score was significantly increased in the JYH-H group and the Fluoxetine group(P<0.01).Nissl staining result showed that the total area of Nissl bodies in hippocampus decreased significantly in the model group compared with that in the control group(P<0.01);compared with that in the model group,the total area of Nissl bodies increased significantly in the JYH-L group and the JYH-H group(P<0.05),and the total area of Nissl bodies also obviously increased in the Fluoxetine group(P<0.01).Immunohistochemistry and Western Blot detection showed that compared with that in the control group,the protein expression ofβ-catenin was significantly decreased in the model group(P<0.01);compared with that in the model group,the protein expression ofβ-catenin was increased in the JYH-L group and the JYH-H group(P<0.05),it was also increased in the Fluoxetine group(P<0.01).The results of QT-PCR showed that compared with that in the control group,the mRNA expression ofβ-catenin was significantly decreased in the model group(P<0.01);compared with that in the model group,the mRNA expression ofβ-catenin was significantly increased in the JYH-L group and the JYH-H group(P<0.05);the mRNA expression ofβ-catenin was also significantly increased in the Fluoxetine group(P<0.01).Conclusion:Jinyuhuan can effectively improve the depression-like behavior of the mice model of depression,which can be achieved by improvingβ-catenin expression.