醒脑解郁方对卒中后抑郁症模型大鼠行为学及海马区p-ERK1/2的影响

Effect of Xingnao Jieyu Recipe on Behavioral and Hippocampus p-ERK1/2 in Post-stroke Depression Model Rats

目的通过观察醒脑解郁方对卒中后抑郁症(post-stroke depression,PSD)大鼠大脑海马区pERK1/2含量及p-ERK1/2表达水平的影响,探讨醒脑解郁方治疗PSD的作用机制。方法健康成年SD大鼠90只,雌雄各半,随机分为6组(正常对照组、模型组、中药早期干预组、西药早期干预组、中药治疗组、西药治疗组),每组15只。在脑缺血模型的基础上采用孤养法及皮下注射利血平法(连续16天)制备PSD模型。中药早期干预组、西药早期干预组大鼠于脑缺血模型制备成功后次日开始干预,连续21天。PSD模型制备成功后中药治疗组、西药治疗组干预治疗,中药早期干预组、西药早期干预组治疗方案不变,连续16天。中药各组均给予醒脑解郁方0.412 5 g/kg溶2 mL蒸馏水灌胃,西药各组均给予氟西汀2.08 mg/kg、拜阿司匹林3.0 mg/kg溶于2 mL蒸馏水内灌胃。空白对照组、模型组给予生理盐水2.0 mL/只灌胃。于实验第2、15、37天观察各组大鼠的体重变化情况、糖水消耗量及旷野试验(包括水平运动和垂直运动)。采用免疫组化法及RT-PCR法检测PSD大鼠大脑海马区p-ERK1/2含量及p-ERK1/2表达水平。结果与正常对照组比较,模型组实验第15、37天体重、糖水消耗量、水平运动和垂直运动降低,p-ERK1/2阳性细胞数及pERK1/2 mRNA的相对表达量减少(P<0.05,P<0.01)。与模型组比较,实验第15、37天中药早期干预组、西药早期干预组体重、糖水消耗量、水平运动和垂直运动升高(P<0.05,P<0.01),实验第37天中药治疗组及西药治疗组大鼠体重、糖水消耗量、水平运动和垂直运动升高(P<0.05,P<0.01)。与模型组比较,中药早期干预组、西药早期干预组、中药治疗组及西药治疗组大鼠海马区p-ERK1/2阳性细胞数及p-ERK1/2 mRNA的相对表达量增加(P<0.05)。结论醒脑解郁方通过提高PSD大鼠模型海马组织内p-ERK1/2的含量并上调p-ERK1/2 mRNA的表达水平,可能是醒脑解郁方治疗PSD的作用机制之一。

Objective To observe the effect of Xingnao Jieyu Recipe on the expression of p-ERK1/2 and p-ERK1/2 in hippocampus of post-stroke depression（ PSD） rats,and to explore the mechanism of Xingnao Jieyu Recipe in the treatment of PSD. Methods Totally 90 healthy adult SD rats were randomly divided into 6 groups,i. e.,the normal group,the model group,the early intervention group of Chinese medicine,the early intervention group of Western medicine,the Chinese medicine treatment group and the Western medicine treatment group,15 in each group. The PSD model was established by solitary method and subcutaneous injection of reserpine（ 16 days） on the basis of cerebral ischemia model. The rats in the early intervention group were treated from the 2 nd day after successful modeling of carebral ischemia for 21 days. The medication stanted after successful modeling of PSD,for 16 days. The rats in each Chinese medicine group were treated with dexamethasone decoction of 0. 4125 g/kg dissolved in 2 m L distilled water. The Western medicine group was given fluoxetine at2. 08 mg/kg,and aspirin 3. 0 mg/kg was dissolved in 2 m L distilled water. The model group was given physiological Saline2. 0 m L. The changes of body weight,sugar consumption and open-field test（ including horizontal movement and vertical movement） were observed on the 2 nd,15 th and 37 th day of the experiment. The expression of p-ERK1/2 and p-ERK1/2 in hippocampus of PSD rats were detected by immunohistochemistry and RT-PCR. Results Compared with the normal group,the body weight,the consumption of sugar solution,the level of horizontal movements and the vertical movement of the model group decreased on day 15,37,and the relative expressions of p-ERK1/2 positive cells and p-ERK1/2 mRNA decreased（P〈0. 01）. Compared with the model group,the body weight,the consumption of sugar solution,the level of horizontal movements and vertical movement increased in the early intervention group on day 15,37（P〈0. 05,P〈0. 01）. In addition,the rats in the Western medicine treatment group and the Chinese medicine treatment group had statistically higher body weight,sugar consumption,horizontal movement and vertical movement（P〈0. 05,P〈0. 01）. Compared with the model group,the expressions of p-ERK1/2 positive cells and p-ERK1/2 mRNA in hippocampus in each treatment group were significantly increased（P〈0. 05）. Conclusion Xingnao Jieyu Recipe may improve the expression of p-ERK1/2 in hippocampus and up-regulate the expression of p-ERK1/2 mRNA in PSD rat model,which may be one of the mechanisms of Xingnao Jieyu Recipe in the treatment of PSD.