疏肝和胃汤对抑郁模型大鼠延髓、脊髓及胃黏膜组织P物质表达的影响

Effects of Shugan Hewei Decoction on the expression of SP in brain, spinal cord and gastric mucosa in depression model rats

目的:观察疏肝和胃汤对抑郁模型大鼠延髓、脊髓及胃黏膜组织P物质(SP)表达的影响,部分揭示该方改善抑郁状态与胃肠功能作用中的SP调节机制。方法:100只大鼠随机分成生理盐水组、模型组、百优解组及疏肝和胃汤大、小剂量组。采用慢性心理应激加孤养法制作抑郁模型,共计造模4周。在第3周,百优解组及疏肝和胃汤大、小剂量组分别予以0.36mg·kg-1·d-1、20、10g·kg-1·d-1给药,生理盐水组及模型组给予等体积0.9%氯化钠溶液,每天分2次灌胃。在第4周结束后,使用内固定法取大鼠延髓迷走神经背核部位的脑、胸髓(T6-T8,根据脊神经定位)及胃黏膜组织,应用免疫组织化学技术检测上述部位SP的表达。结果:与生理盐水组比较,模型组大鼠延髓、脊髓中SP含量明显升高,胃黏膜SP含量明显下降(P<0.01);治疗2周后(造模第4周),与模型组比较,疏肝和胃汤大、小剂量组和百优解组大鼠延髓、脊髓组织中SP含量明显下降,胃黏膜SP含量明显上升(P<0.05,P<0.01);其中,疏肝和胃汤大剂量组与百优解组脊髓中SP含量比较无显著性差异,但延髓与胃黏膜中SP含量与百优解组相比,有显著性差异(P<0.05)。结论:疏肝和胃汤可能是通过降低延髓、脊髓中SP的表达,升高胃黏膜中SP的表达,双向调节"脑(延髓)-脊髓-胃"脑肠轴通路中SP的含量,达到改善抑郁状态与胃肠功能的作用。

Objective： To observe the effects of Shugan Hewei Decoction （SHD） on the expression of substance P （SP） in brain （medulla oblongata）, spinal cord and gastric mucosa in depression model rats, so as to reveal the possible mechanism of SHD to relieve depression and improve gastrointestinal function. Methods： Totally 100 wistar rats were randomized into the normal saline group, model group, fluoxetine group and the high, low dosage of SHD group, with 20 in each group. The depression models were established with chronic unpredictable mild stress （CUMS） and separation according to related references for 4 weeks. At the 3rd week, the model and each treatment group began to medication. Fluoxetine group and high, low dosage of SHD groups were given Fluoxetine and high, low dosage of Shugan Hewei Decoction by 0.36mg·kg^-1·d^-1, 20, 10g·kg^-1·d^-1 in weights through introgastric administration respectively, twice a day; the normal saline group and model group were given the same volume normal saline. Every group must be given continuous course treatment for fourteen days. At the end of the fourth week, the internal fixation method was used to take brain （medulla oblongata vagus nerve nucleus） tissue, spinal cord tissue （T6- T8） and gastric mucosa tissue. The method of immunohistochemistry （IHC） was used to detect the expression of SP in the above tissues. Results： Comparing with the normal saline group, the content of SP increased significantly in brain （medulla oblongata） and spinal cord of model rats （P〈0.01）, the content of SP decreased obviously in gastric mucosa （P〈0.01）. Comparing with the model group, the content of SP reduced significantly in brain （medulla oblongata） and spinal cord of high, low dosage of SHD groups and fluoxetine group （P〈0.05, P〈0.01）, the content of SP raised obviously in gastric mucosa （P〈0.05, P〈0.01）. In addition, the effect of high dosage of SHD was equal to fluoxetine group in spinal cord, while the former was better than the later in medulla oblongata and gastric mucosa （P〈0.05）. Conclusion： SHD had bidirectional regulation effects on the expression of SP in the signal path of brain-gut axis-＇brain （medulla oblongata）-spinal cord -gastric mucosa＇, which may be part of the mechanism for relieving depression and improving gastrointestinal function.