疏肝和胃汤对抑郁模型大鼠PFC-NAc-VTA神经环路DA含量的影响

Effects of Shugan Hewei Decoction on dopamine content in PFC-NAc-VTA neural circuit of depression model rats

目的:观察疏肝和胃汤对抑郁模型大鼠脑部前额叶皮层(PFC)-伏隔核(NAc)-腹侧被盖区(VTA)神经环路多巴胺(DA)含量的影响,探讨疏肝和胃汤的抗抑郁作用机制。方法:120只大鼠随机分成空白组,模型组,疏肝和胃汤低、中、高剂量组,氟西汀组,每组20只,慢性不可预知性温和应激结合孤养法制作抑郁大鼠模型,共计造模4周后,疏肝和胃汤低、中、高剂量组分别予3.67、7.34、14.68g·kg-1·d-1给药,氟西汀组按1.58mg·kg-1·d-1给药,空白组及模型组给予等体积0.9%氯化钠溶液,每天灌胃1次,共计7d。在第5周结束后,根据大鼠脑立体定位图取大鼠脑PFC区、NAc区及VTA区组织,采用高效液相色谱法检测各脑区DA的含量。结果:与空白组比较,模型组大鼠PFC区、NAc区及VTA区DA含量均明显降低(P<0.01);治疗1周后,疏肝和胃汤中、高剂量组及氟西汀组大鼠PFC区DA含量升高,疏肝和胃汤各剂量组及氟西汀组NAc区DA含量升高,疏肝和胃汤低、中剂量组及氟西汀组大鼠VTA区DA含量升高,与模型组比较均有显著性差异(P<0.05,P<0.01);其中,PFC区疏肝和胃汤高剂量组与氟西汀组比较,NAc区疏肝和胃汤中剂量组与氟西汀组比较,无显著性差异,而VTA区疏肝和胃汤低、中剂量组与氟西汀组比较,差异有统计学意义(P<0.01)。结论:疏肝和胃汤可能是通过增加PFC区、NAc区及VTA区DA的表达,整体调节PFC-NAc-VTA神经环路中DA的含量,达到改善抑郁样行为的作用。

Objective： To observe the effects of Shugan Hewei Decoction on dopamine（DA） content in prefrontal cortex（PFC）-nucleus accumbens（NAc）-ventral tegmental area（VTA） neural circuit of depression model rats, and to explore the possible anti-depression mechanism of Shugan Hewei Decoction. Methods： One hundred and twenty rats were randomized divided into the blank control group, the model group, the low, middle and high dose Shugan Hewei Decoction group, and the fluoxetine group, with twenty rats in each group. The depression rats model was established with chronic unpredictable mild stress（CUMS） combined with social isolation. Four weeks after modeling, the low, middle and high dose Shugan Hewei Decoction groups were respectively intervened with Shugan Hewei Decoction with a dosage of 3.67, 7.34, 14.68 g/kg, the fluoxetine group was intervened with fluoxetine with a dosage of 1.58 mg/kg, the blank control group and model group were given the same volume normal saline. Each group was given intragastric administration for seven days, once a day. At the end of the fifth week, the rat brain tissues in PFC, NAc and VTA were taken out based on rat brain stereogram, and the method of high performance liquid chromatography（HPLC） was used to detect the DA content in PFC, NAc and VTA. Results： Compared with the blank control group, the DA content of PFC, NAc and VTA were all decreased obviously in model group（P〈0.01）. One week after treatment, the DA content of PFC in the middle and high dose Shugan Hewei Decoction group and fluoxetine group increased, and DA content of NAc in the low, middle,high dose Shugan Hewei Decoction group and fluoxetine group increased, and DA content of VAT in the low, middle dose Shugan Hewei Decoction group and fluoxetine group increased. There were all significant differences, comparing with the model group（P〈0.05, P〈0.01）. There was no significant difference in DA content of PFC between the high dose Shugan Hewei Decoction group and the fluoxetine group, and the same in DA content of NAc between the middle dose Shugan Hewei Decoction group and the fluoxetine group. While there was significant difference of DA content among the low, middle dose Shugan Hewei Decoction group and the fluoxetine group in VTA（P〈0.01）. Conclusion： Shugan Hewei Decoction playing a role of improving depression behavior may be by increasing the expression of DA in PFC, NAc and VTA, and it integrally regulates the DA content in PFC-NAc-VTA neural circuit.