自拟健脾益气方药的抗抑郁作用及其机制研究  

Study on antidepressant effect and mechanism of self-made prescription of strengthening spleen and replenishing Qi

作　　者：牛倩[1] 詹合琴[1] 蒋燕[2] 赵正杭 刘会如 胡雨 NIU Qian;ZHAN He-qin;JIANG Yan;ZHAO Zheng-hang;LIU Hui-ru;HU Yu(College of Pharmacy;the Nursing College,Xinxiang Medical University, Xinxiang, Henan 453003, China;Dept of Pharmacology,School of Basic Medical Sciences,Xi＇an Jiaotong University Health Science Center, Xi＇an 710061, China)

机构地区：[1]新乡医学院药学院,河南新乡453003 [2]新乡医学院护理学院,河南新乡453003 [3]西安交通大学医学部基础医学院药理学系,陕西西安710061

出　　处：《中国药理学通报》2018年第6期867-872,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81470510;81170597);河南省自然科学基金资助项目(No 162300410219);新乡市重点科技攻关计划资助项目(No ZG14006)

摘　　要：目的 探讨自拟健脾益气方药(SMP-SSRQ)的抗抑郁作用及其机制。方法 建立慢性不可预知性温和应激(chronic unpredictable mild stress,CUMS)抑郁小鼠模型,随机分为正常组、模型组、SMP-SSRQ低、中、高剂量组(8、16、32 mg·kg^(-1)),每组12只。正常对照组与模型组动物给予同体积的生理盐水,SMP-SSRQ各剂量组分别给予相应剂量的药物。均采用灌胃给药,每天2次,连续给药2周。通过旷场、糖水消耗、强迫游泳和悬尾等实验检测动物的不同行为学指标;采用实时荧光定量PCR和Western blot分别检测各组小鼠大脑前额叶皮质和海马组织中免疫球蛋白超家族11(Igsf11)、蛋白质二硫键异构酶2(Pdia2)、生育酚结合蛋白(Sec14l2)mRNA及蛋白水平的表达变化。结果 与模型组比较,SMP-SSRQ各治疗组均可增加抑郁小鼠的水平移动格数、直立次数以及糖水偏好指数(P<0.05),降低强迫游泳和悬尾不动时间,明显改善抑郁症状;低、高剂量的SMPSSRQ能明显降低抑郁小鼠大脑皮层前额叶与海马组织中Igsf11、Pdia2、Sec14l2 mRNA及蛋白的表达水平,与模型组比较差异有显著性(P<0.05)。结论 SMP-SSRQ可有效改善小鼠的抑郁行为,机制可能与其下调小鼠皮层和海马组织中的Igsf11、Pdia2、Sec14l2的mRNA及其蛋白水平有关。Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi（SMP-SSRQ）. Methods The depression model of chronic unpredictable mild stress（CUMS） was established in mice. The animals were randomly divided into control group,model group,SMP-SSRQ low,middle and high dose groups（8,16,32 mg·kg（-1））,with 12 mice for each group. The control group and the model group were given the same volume of saline,and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were determined by open field experiment,sugar consumption test,forced swimming test and tail suspension test.Quantitative real-time PCR（q PCR） and Western blot were respectively performed to detect mRNA and protein expression levels of Igsf11,Pdia2 and Sec14l2 in prefrontal cortex and hippocampus. Results Compared with model group,depressed mice＇s horizontal mobile score,upright number and the sugar water preference index increased and FST as well as TST decreased in all SMP-SSRQ groups（P 〈 0. 05）. The depression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression level of Igsf11,Pdia2 and Sec14l2 in the prefrontal cortex and hippocampus of the depressed mice,presenting significant statistical difference compared with model group（P 〈 0. 05）. Conclusions SMP-SSRQ can effectively improve mouse depressive behavior,and its mechanism may be related to the down-regulation of Igsf11,Pdia2 and Sec14l2 in mouse prefrontal cortex and hippocampus.

关 键 词：自拟健脾益气方药 抑郁症 前额叶皮质 海马 免疫球蛋白超家族11 蛋白质二硫键异构酶2 生育酚结合蛋白 

分 类 号：R-332[医药卫生] R289.5