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目的:观察逍遥散和6-氰基-7-硝喹啉-2,3-双酮(CNQX)对慢性束缚应激所致肝郁脾虚证大鼠中枢AMPA受体及其相关蛋白表达的影响,探讨逍遥散的作用机制。方法:将100只雄性SD大鼠随机分为正常组(A组)、假手术组(B组)、模型组(C组)、逍遥散组(D组)、CNQX组(E组)和逍遥散+CNQX组(F组)。C、D、E、F组大鼠通过连续21d慢性束缚应激建立肝郁脾虚证候模型,D、F组大鼠每天束缚前灌服逍遥散5.32g/kg,E、F组大鼠隔天右侧杏仁核区微量注射α-氨基羟甲基恶唑丙酸(AMPA)受体拮抗剂CNQX 0.5μL。各组动物第22d处死,免疫组化方法检测海马CA1区、CA3区、基底外侧杏仁核(BLA)谷氨酸受体2/3(GluR2/3)、N-乙基顺丁烯二酰亚胺敏感性的融合蛋白(NSF)、PKC作用蛋白1(PICK1)水平。结果:模型大鼠GluR2/3在海马CA1、CA3区明显减少,BLA区明显增加;NSF在海马CA1、CA3区有减少趋势;PICK1在海马CA3区明显增加。CNQX和逍遥散对模型大鼠GluR2/3 PICK1在海马的变化均有调节作用。逍遥散联合CNQX作用于慢性束缚应激大鼠与单独使用逍遥散或CNQX后呈现一致性。结论:调节AMPA受体及其相关蛋白在海马各区和杏仁核的兴奋性至少是逍遥散调节突触可塑性、进一步治疗应激和抑郁的作用途径之一。
AIM: To observe the effects of Xiaoyao San and 6-Cyano-7-nitroquinoline-2,3-dione (CNQX) on the expression of AMPA receptor and its related proteins in the rats with liver-qi and spleen deficiency syndrome induced by chronic restraint stress , Explore the role of Xiaoyaosan mechanism. Methods: 100 male SD rats were randomly divided into normal group (A group), sham operation group (B group), model group (C group), Xiaoyao powder group (D group), CNQX group (E group) Casual + CNQX group (F group). Rats in groups C, D, E and F were challenged with chronic restraint stress for 21 days to establish a model of stagnation of liver-qi and spleen deficiency. Rats in groups D and F were fed with Xiaoyaosan 5.32g / kg daily before shackling, rats in groups E and F The right amygdaloid nucleus area was injected with 0.5 μL of CNQX, an α-amino hydroxymethyl methyloxazole propionic acid (AMPA) receptor antagonist. Animals in each group were killed on the 22nd day, and the expressions of glutamate receptor 2/3 (GluR2 / 3), N-ethyl maleate Amine-sensitive fusion protein (NSF), PKC-responsive protein 1 (PICK1) levels. Results: GluR2 / 3 significantly decreased in CA1 and CA3 regions of hippocampus and markedly increased in BLA; NSF decreased in CA1 and CA3 regions of hippocampus; PICK1 increased significantly in CA3 region of hippocampus. CNQX and Xiaoyao San had a regulatory effect on the changes of GluR2 / 3 PICK1 in the hippocampus of model rats. Xiaoyaosan combined CNQX effect on chronic restraint stress rats and alone or Xiaoyao San or CNQX consistent. CONCLUSION: The excitability of AMPA receptor and its related proteins in hippocampus and amygdala is at least one of the mechanisms by which Xiaoyaosan regulates synaptic plasticity and further treats stress and depression.