逍遥散调控肝窦内皮窗孔改善大鼠抑郁样行为的机制研究

摘要

【目的】探讨逍遥散对大鼠抑郁样行为的作用及其调节机制。【方法】将雄性Wistar大鼠随机分为正常组、模型组、逍遥散组（剂量为19 g·kg－1·d－1）和氟西汀组（剂量为2 mg·kg－1·d－1）。采用慢性不可预测轻度应激（chronic unpredictable mild stress， CUMS）诱导大鼠抑郁样行为，旷场实验观察逍遥散对抑郁样行为的作用， Luminex液相芯片分析系统检测大鼠血清细胞因子，电镜观察大鼠肝窦内皮窗孔数量和大小， Western blot法分别检测肝组织中吲哚胺2，3-双加氧酶（indoleamine 2，3-dioxygenase， IDO）和色氨酸2，3-双加氧酶（tryptophan 2，3-dioxygenaes， TDO）表达。【结果】逍遥散可显著增加大鼠糖水消耗、爬格数和直立数，显著降低血清TNF-α、 IL-6水平，增加窗孔数量与大小，改善肝窦内皮血管化倾向，并降低TDO和IDO的表达（均P＜0.05或P＜0.01)。【结论】逍遥散可显著改善大鼠抑郁样行为，可能与其降低炎症因子、抑制IDO通路、改善肝窦内皮功能作用有关。%Objective To observe the effectiveness and mechanism of Xiaoyao San (Xiaoyao Powder for Soothing Liver and Relieving Depression) in improving depression-like behavior of rats. Methods Male Wistar rats were randomized into normal group, model group, Xiaoyao San (1.9 g·kg-1·d-1) group, and fluoxetine (2 mg·kg-1·d-1) group. The rats were exposed to chronic unpredictable mild stress ( CUMS) to induce rat depression-like behavior. Field test was performed for the observation of effect of Xiaoyao San on rat depression-like behavior, Luminex liquid chip system was applied to detect the serum cytokines, and the amount and size of rat hepatic sinusoidal endothelial window were examined under electron microscope, and hepatic indoleamine 2, 3-dioxygenase ( IDO) and tryptophan 2, 3 -dioxygenaes ( TDO) expression levels were detected by immunohistochemical and Western blot methods. Results Xiaoyao San showed obvious effect on increasing sugar water consumption, the number of crossing the blocks and erection frequency in rats, decreasing serum levels of tumor necrosis factor alpha ( TNF-α) and interleukin 6 ( IL-6) , increasing the amount of hepatic sinusoidal endothelial window, promoting hepatic sinusoidal endothelial vascularization, and reducing TDO and IDO expression ( P<0.05 or P<0.01). Conclusion Xiaoyao San exerts obvious effect on improving rat depression-like behaviors, and the mechanism is probably related with the decrease of inflammatory factors, inhibition of IDO pathway, and improvement of hepatic sinusoidal endothelial function.