逍遥散调节肝郁脾虚大鼠中枢AMPA受体及相关蛋白的机制研究  

Changes of AMPA receptors and related protein in immobilization stress rats and effect of XiaoYaoSan

作　　者：梁媛[1,2] 郭晓玲[2] 岳广欣[1] 张婷[2] 刘群[2] 张燕[2] 高青青[2] 刘月芸[2] 陈家旭[2] 

机构地区：[1]中国中医科学院基础所,北京100700 [2]北京中医药大学中医诊断教研室,北京100029

出　　处：《中华中医药杂志》2011年第1期69-74,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金课题(No.30672578);国家杰出青年科学基金课题(No.30825046)~~

摘　　要：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。Objective： To observe effect of XiaoYaoSan on AMPA receptors and related protein in rats with liver stagnation and spleen deficiency syndrome caused by chronic immobilization stress after CNQX injected into the right Amygdale.Methods：100 male SD rats were randomly divided into normal control group（A group）,sham-operation group（B group）,model group（C group）,XiaoYaoSan group（D group）,CNQX group（E group） and XaoYaoSan＋CNQX group（F group）.Rats of C,D,E,F groups were restrained 3 hours per day for 21days to establish model of liver stagnation and spleen deficiency syndrome caused by chronic immobilization stress（CIS）.XiaoYaoSan was administered from the first day to the 21st day before the immobilization in D and F groups.On the 1st,4th,7th,10th,13th,16th,19th,21st day,unilateral intra-amygdala infusion of the AMPA receptor antagonist CNQX（0.5μL） was administered to rats of E and F groups.Rats were executed and GluR2/3,NSF,PICK1 level was detected by immunohistochemical stain on the 22nd day.Results： in immobilization stress 21 days rats,GluR2/3 products significant decreased in CA1,CA3,but increased in BLA;NSF had a decreased trend in hippocampus;PICK1 increased significantly in all regions of hippocampus.CNQX increased the expression of GluR2/3 in CA1,CA3,but decreased them in BLA;had a significant positive regulation on PICK1 increase in CA1,CA3.Xiaoyaosan had a regulatory role in GluR2/3 decrease and regulated PICK1 from increase to normal in CA1,CA3.Conclusion： Xiaoyaosan may effectively regulate the balance of the excitability of hippocampus and amygdale（AMPA receptors and related proteins）,which may be one of the central mechanisms of regulating the stress.

关 键 词：慢性束缚应激 肝郁脾虚 逍遥散 6-氰基-7-硝喹啉-2 3-双酮 海马 杏仁核 α-氨基羟甲基恶唑丙酸受体 

分 类 号：R285.5[医药卫生—中药学]