百地枣合剂对抑郁症模型大鼠海马组织中β-catenin蛋白及GSK-3β mRNA表达的影响

Effects of Baidizao Mixture (百地枣合剂) on β-catenin Protein and GSK-3β mRNA Expression in Hippocampus of Depression Model Rats

目的探讨百地枣合剂治疗抑郁症的可能作用机制。方法60只Wistar大鼠随机分为空白组、模型组、盐酸氟西汀组和百地枣合剂高、中、低剂量组,每组10只。除空白组外其余各组大鼠采用慢性应激性刺激结合孤养29天建立抑郁症大鼠模型。实验第8天开始,百地枣合剂低、中、高剂量组分别给予浓度为0.7、1.4、2.8g/ml百地枣合剂,盐酸氟西汀组给予浓度为0.36mg/ml盐酸氟西汀混悬液,模型组和空白组给予生理盐水,各组按照1ml/100g体重灌胃,连续灌胃21天。分别于实验第0、7、29天各组大鼠进行旷场试验、糖水偏好实验,观察大鼠水平运动距离、站立次数,计算糖水偏好率;采用尼氏染色观察大鼠海马组织病理,并检测海马组织中糖原合成酶激酶3β(GSK-3β)mRNA和β-连环蛋白(β-catenin)表达。结果实验第29天,与空白组比较,模型组大鼠水平运动距离、站立次数降低,糖水偏好率下降,海马组织β-catenin蛋白表达降低、GSK-3βmRNA表达升高(P<0.05或P<0.01);与模型组比较,盐酸氟西汀组和百地枣合剂高剂量组大鼠水平运动距离、站立次数增加,糖水偏好率上升,海马组织β-catenin蛋白表达升高,GSK-3βmRNA降低(P<0.05或P<0.01)。百地枣合剂高剂量组大鼠糖水偏好率、海马组织β-catenin蛋白表达较百地枣合剂中、低剂量组升高(P<0.01)。结论百地枣合剂可改善抑郁大鼠行为,其机制可能与减少海马中GSK-3βmRNA、增加β-catenin表达有关,且以高剂量效果最佳。

Objective To explore the possible mechanism of Baidizao Mixture(百地枣合剂) in treating depression. Methods A total of 60 Wistar rats were randomly divided into a blank group, a model group, a fluoxetine hydrochloride group and a Baidizao Mixture high, medium and low dose groups, with 10 rats in each group. Except the blank group, rats were treated with chronic stress stimulation and orphanage for 29 days to establish a depression rat model. Beginning on the 8 th day of the experiment, the low, medium and high doses of Baidizao Mixture were given Baidizao Mixture at a concentration of 0.7, 1.4, and 2.8 g/ml respectively, and the fluoxetine hydrochloride group was given a concentration of 0.36 mg/ml fluoxetine hydrochloride suspension. The model group and the blank group were given normal saline, and all groups were given intragastric administration with 1 ml/100 g body weight for 21 consecutive days. On the baseline, 7 th, and 29 th day of the experiment, rats in all groups were subjected to an open field test and a sugar water preference test. The horizontal movement distance and standing times of the rats were observed. The sugar water preference rate was caculated. The Nissl stain was used to observe the hippocampal histopathology of the rats. Glycogen synthase kinase 3β(GSK-3β) mRNA and β-catenin expression in hippocampus were detected. Results On the 29 th day of the experiment, compared with the blank group, the horizontal movement distance and the number of standing of rats in the model group decreased, the sugar water preference rate decreased, the β-catenin protein expression in the hippocampus tissue decreased, and GSK-3β mRNA expression increased(P<0.05 or P<0.01);Compared with the model group, the rats in the fluoxetine hydrochloride group and the Baidizao Mixture high dose group increased horizontal movement distance and standing times, increased sugar water preference, increased β-catenin protein expression in hippocampus, and reduced GSK-3β mRNA(P<0.05 or P<0.01). The sugar and water consumption rate and β-catenin protein expression in hippocampus of the high dose Baidizao Mixture group were increased than those in the medium-dose and low-dose Baidizao Mixture group(P<0.01). Conclusion Baidizao Mixture can improve the behavior of depressive rats. The mechanism may be related to reducing GSK-3β mRNA and increasing β-catenin expression in hippocampus, and the high dose group showed the best result.