疏肝方改善柔证大鼠抑郁样行为神经内分泌作用研究  

Neuroendocrine Mechanism of Shugan Decoction in Improving Depressive-like Behaviors in Gentle Syndrome Rats

作　　者：裴雪梅 张成[2] 赵鹏[1] 原晨 柳红良 李健[2] PEI Xuemei;ZHANG Cheng;ZHAO Peng;YUAN Chen;LIU Hongliang;LI Jian(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 101100,China;Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Shunyi Hospital,Beijing Hospital of Traditional Chinese Medicine,Beijing 101399,China)

机构地区：[1]北京中医药大学东直门医院,北京101100 [2]中国中医科学院广安门医院,北京100053 [3]北京中医医院顺义医院,北京101399

出　　处：《世界中医药》2024年第21期3282-3288,共7页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81704057);中国中医科学院优秀青年科技人才专项(ZZ13-YQ-024)。

摘　　要：目的:探索疏肝方改善抑郁样行为的神经内分泌作用。方法:将大鼠按照随机数字表法随机分为正常组、模型组、西药组和中药组,采用不可预见温和应激(CUMS)法制备柔证模型,西药组给予盐酸氟西汀、中药组给予疏肝方。记录体质量、糖水实验、旷场试验结果,干预后检测外周血及下丘脑促肾上腺皮质激素(ACTH)、皮质醇(CORT)、5-羟色胺(5-HT)和去甲肾上腺素(NE)水平,海马、杏仁核一氧化氮(NO)水平,海马、皮层脑源性神经营养因子(BDNF)、环磷腺苷效应元件结合蛋白(CREB)、磷酸化细胞外调节蛋白激酶(p-ERK)、c-fos、c-jun和磷酸化环磷腺苷效应元件结合蛋白(p-CREB),杏仁核c-fos、c-jun蛋白水平,海马、杏仁核BDNF、c-fos、c-jun mRNA表达水平。结果:造模第21天,与模型组比较,西药组和中药组体质量、旷场试验总路程及糖水偏爱度均明显升高(P<0.05)。与模型组比较,西药组和中药组外周血ACTH、CORT水平明显下降,下丘脑5-HT、NE水平明显升高(P<0.05);西药组和中药组杏仁核、海马c-fos、c-jun、西药组皮层c-fos、c-jun、中药组皮层c-fos均明显下降(P<0.05),皮层、海马p-ERK、BDNF明显升高(P<0.05)。中药组皮质BDNF、海马p-CREB高于西药组(P<0.01及P<0.05)。西药组和中药组海马c-fos、c-jun mRNA、NO,杏仁核c-jun mRNA及NO水平均明显下降(P<0.05或P<0.01),海马及杏仁核BDNF mRNA明显升高(P<0.05)。结论:疏肝汤明显改善柔证大鼠抑郁样行为,其作用机制与纠正下丘脑-垂体-肾上腺(HPA)轴激活异常、调节下丘脑5-HT、NE水平、在蛋白或mRNA不同层面对c-fos、c-jun、NO及调控促分裂原活化的蛋白激酶(Mapk)通路影响BDNF水平改善神经细胞再生和修复能力有关。Objective:To explore the neuroendocrine effects of Shugan Decoction in improving depressive-like behaviors.Methods:Rats were randomly divided into normal,model,Western medicine,and Chinese medicine groups using a random number table.A gentle syndrome model was induced by chronic unpredictable mild stress(CUMS).The Western medicine group was treated with fluoxetine hydrochloride,while the Chinese medicine group was treated with Shugan Decoction.Body weight,sucrose preference test,and open field test results were recorded.After intervention,peripheral blood and hypothalamic levels of adrenocorticotropic hormone(ACTH),cortisol(CORT),serotonin(5-HT),and norepinephrine(NE)were measured.The levels of nitric oxide(NO)in the hippocampus and amygdala,brain-derived neurotrophic factor(BDNF),cyclic adenosine monophosphate response element-binding protein(CREB),phosphorylated extracellular signal-regulated kinase(p-ERK),c-fos,c-jun,and phosphorylated CREB(p-CREB)in the hippocampus and cortex were also detected.Additionally,the protein levels of c-fos and c-jun in the amygdala and mRNA expression of BDNF,c-fos,and c-jun in the hippocampus and amygdala were analyzed.Results:On the 21st day of modeling,compared with the model group,both the Western medicine and Chinese medicine groups showed significant increases in body weight,total distance in the open field test,and sucrose preference(P<0.05).The levels of peripheral blood ACTH and CORT were significantly lower,while hypothalamic 5-HT and NE levels were significantly higher in the Western medicine and Chinese medicine groups compared with the model group(P<0.05).Protein levels of c-fos and c-jun in the amygdala and hippocampus in the Western medicine and Chinese medicine groups,cortical c-fos and c-jun in the Western medicine group,and cortical c-fos in the Chinese medicine group were significantly reduced(P<0.05).Phosphorylated ERK(p-ERK)and BDNF in the cortex and hippocampus were significantly increased(P<0.05).The Chinese medicine group showed higher cortical BDNF and hip

关 键 词：疏肝方 柔证 大鼠 抑郁样行为 神经 内分泌 作用机制 研究 

分 类 号：R289.9[医药卫生—方剂学] R259[医药卫生—中药学]