人参皂苷Rg1对慢性应激抑郁模型大鼠谷氨酸及其受体表达的影响

目的:观察人参皂苷Rg1对慢性应激抑郁模型大鼠脑内海马、前额叶皮质区谷氨酸及其不同类型受体表达的影响,探讨其潜在的抗抑郁机制。方法:将SD大鼠随机分为5组:正常组、模型组、氟西汀组(10 mg·kg-1)、人参皂苷Rg1低、高剂量组(25、50 mg·kg-1)。采用慢性不可预见性温和应激的方法建立抑郁大鼠模型,于造模同时灌胃给药,共21天。造模结束后采用Morris水迷宫和旷场实验评价大鼠的抑郁样行为,HE染色观察大鼠海马、前额叶皮质区病理改变情况,HPLC法检测谷氨酸含量,Western-blotting法检测离子型谷氨酸受体NMDAR1、代谢型谷氨酸受体mGluR1的蛋白表达情况。结果:与正常组比较,模型组大鼠抑郁样行为显著,海马、前额叶皮质区均存在较为明显的损伤,谷氨酸含量显著升高,NMDAR1、mGluR1蛋白表达均显著上调;在给予人参皂苷Rg1干预后,模型大鼠的抑郁样行为得到缓解,海马、前额叶皮质区损伤减轻,谷氨酸含量下降,NMDAR1、mGluR1蛋白表达水平明显逆转。结论:人参皂苷Rg1对大鼠抑郁症状有明显的改善作用,并能减轻海马和前额叶皮质损伤,其机制可能与调节脑内谷氨酸含量,并抑制其受体表达有关。

Effect of ginsenoside Rg1 on expression of glutamate and its receptor in chronic stress depression model rats

OBJECTIVE To observe the effect of ginsenoside Rg1 on the expression of glutamate and its receptor in the hippocampus and prefrontal cortex of chronic stress-induced depression rats and to explore its possible antidepressant mechanism.METHODS SD rats were randomly divided into normal, model, fluoxetine (10 mg·kg^-1), low, high dose of ginsenoside Rg1 (25, 50 mg·kg^-1). The chronic unpredictable mild stress was used to establish depression model, which was administered intragastrically at the same time for 21 days. Morris water maze and open field experiments were used to evaluate the depressive behaviors. HE staining was used to observe the pathological changes of hippocampus and prefrontal cortex. Content of glutamic acid was detected by HPLC, and Western-blotting was used to detect protein expressions of ionotropic glutamate receptor NMDAR1 and metabotropic glutamate receptor mGluR1.RESULTS Compared with control, the depression-like behavior was significant in model rats, hippocampus and prefrontal cortex had obvious damage,glutamic acid content was significantly increased, and the expressions of NMDAR1 and mGluR1 protein were significantly upregulated. After administration of ginsenoside Rg1, the depression-like behaviors of model rats were reduced, damage in hippocampus and prefrontal cortex was reduced, glutamate decreased, and the NMDAR1, mGluR1 protein levels were significantly reversed.CONCLUSION Ginsenoside Rg1 can significantly improve the depressive symptoms of rats, and reduce the damage of hippocampus and prefrontal cortex, its mechanism might be related to the regulation of brain glutamate content and inhibition of its receptor expression.