逍遥散对嗅球摘除抑郁模型大鼠的抗抑郁作用机制研究  

Study on the mechanisms of antidepressant effect of Xiaoyao Powder in olfactory bulbectomized depression rats

作　　者：何敏[1] 刘金伟[2] 龚锡平[1] 刘蓉[1] 武志强[1] 王学[1] 阙昌田 曾南[1] 

机构地区：[1]成都中医药大学药学院、中药资源系统研究与开发利用省部共建国家重点实验室培育基地,成都611137 [2]武汉市第一医院,武汉430000

出　　处：《中药药理与临床》2014年第5期14-17,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省教育厅自然科学重点项目(13ZA028);四川省科技厅中药药理四川省青年科技创新研究团队(2014TD0007)

摘　　要：目的:观察逍遥散对嗅球摘除抑郁模型大鼠血清单胺类神经递质水平,及海马与皮质部位5-HT1A、5-HT2A mRNA表达、5-HT1A蛋白表达的影响,探讨其抗抑郁作用机制。方法:手术摘除方法建立SD大鼠的嗅球摘除抑郁模型。逍遥散三个剂量(30g/kg、15g/kg、7.5g/kg)和阿米替林(0.01g/kg)连续灌胃给药4周。高效液相-电化学法测定大鼠血清NE、AD、DA与5-HT水平,Real-time PCR测定大鼠海马及皮质部位5-HT1A、5-HT2A mRNA表达,Western-blotting法测定5-HT1A受体蛋白表达水平。结果:与正常组或假手术组比较,嗅球摘除抑郁模型大鼠血清NE、5-HT含量显著降低,海马与皮质部位5-HT1A mRNA表达水平相对下调,5-HT2A mRNA表达相对上调,5-HT1A蛋白表达水平明显下调,提示该模型动物存在单胺类神经递质水平紊乱表现。与模型组比较,逍遥散(30g/kg、15g/kg)提高血清NE、AD含量,30g/kg逍遥散提高5-HT含量,7.5g/kg亦提高血清NE含量;逍遥散(30g/kg、15g/kg)显著上调模型大鼠海马、皮质部位5-HT1A受体蛋白表达量,对5-HT1A、5-HT2A mRNA的异常表达有一定改善作用,7.5g/kg剂量明显上调皮质5-HT1A mRNA表达水平。结论:逍遥散对嗅球摘除抑郁模型大鼠的抗抑郁作用发挥与提高血清单胺类神经递质(NE、AD、5-HT)水平,上调海马、皮质部位5-HT1A mRNA表达及5-HT1A受体蛋白表达水平有关,表明逍遥散的作用机制与调控5-HT能神经功能有关。Objective： Observe the effects of Xiaoyao Powder on serum levels of monoamine neurotransmittes,the expressions of 5-HT1 A /5-HT2 A mRNA and 5-HT1 A protein in hippocampus and cortex areas in olfactory bulbectomy depression model rats,so as to investigate the anti depressive mechanism. Methods： The depression model was produced by the OB operation on SD rats. Xiao yaosan（ 30 g / kg,15 g / kg,7. 5g /kg） and amitriptyline（ 0. 01 g / kg） were given by intragastric administration for 4 weeks. The level of monoamine neurotransmitters in serum were detected by HPLC-ECD,and the expression of 5-HT1 A /5-HT2 A mRNA in the hippocampus and cortex were detected by RT-PCR. The expression of 5-HT1 A receptor protein was detected by western-blot. Results： Compared with the normal group or sham operation group,the level of 5-HT and NE in olfactory bulbectomized rats significantly decreased,meanwhile the expression of 5-HT1 A mRNA was relatively down regulated,while the expression of 5-HT2 A mRNA was relatively up regulated,and the expression of 5-HT1 A protein was significantly down regulated. Compared with the model group,Xiaoyao Powder（ 30 g / kg,15 g / kg） increased the serum contents of NE and AD,and the content of 5-HT was significantly increased by Xiaoyao Powder under the dose of 30 g / kg,meanwhile the content of NE in serum was also increased under the dose of 7. 5 g / kg. Xiaoyao Powder（ 30 g / kg,15 g / kg） could significantly up-regulated the expression of 5-HT1 A receptor protein in hippocampus and cortex in model rats,and improved the abnormal expression of 5-HT2 A /5-HT1 A mRNA which significantly up regulated the expression of 5-HT1 A mRNA in cortex under the dose of 7. 5g / kg）. Conclusion： Xiaoyao Powder showed the antidepression effect in olfactory bulbectomized rats,which the mechanism was related to increasing the levels of monoamine neurotransmitters（ NE,AD,5-HT）,and up regulating the expression of 5-HT1 A mRNA / protein in hippocampus and cortex. It indicated that the antidepre

关 键 词：逍遥散 嗅球摘除抑郁模型大鼠 单胺类神经递质 5-HT1A 5-HT2A 

分 类 号：R285[医药卫生—中药学]