摘要
目的:基于“肝脑相关”理论探讨柴胡疏肝散对慢性不可预知性应激模型(CUMS)大鼠眶额叶皮层(OFC)的保护作用及其机制。方法:制备CUMS模型,将大鼠随机分为正常对照组、模型组、艾司西酞普兰(10.5 mg/kg)阳性对照组及柴胡疏肝散低(3.15 g/kg)、中(6.3g/kg)、高(12.6 g/kg)剂量组,正常对照组和模型组给予等体积生理盐水。采用小动物超声影像系统记录肝静脉和门静脉血流动力学;采用苏木素-伊红(HE)染色观察大鼠OFC组织病理学变化;免疫荧光检测大鼠OFC组织小胶质细胞标志物Iba-1表达;Western blot检测OFC中BDNF、TrkB、p-ERK蛋白表达。Real-time PCR检测OFC中BDNF、TrkB、p-ERK mRNA的表达。结果:与模型组比较,艾司西酞普兰组和柴胡疏肝散高剂量组大鼠肝静脉和门静脉血流流速、血流流量均显著改善(P<0.05或P<0.01);艾司西酞普兰组和柴胡疏肝散高剂量组大鼠OFC组织细胞病理形态明显改善。同时艾司西酞普兰和高剂量柴胡疏肝散可显著减少模型大鼠OFC中Iba-1的产生并显著升高模型大鼠OFC中BDNF、TrkB、p-ERK mRNA及蛋白表达(P<0.05或P<0.01)。结论:柴胡疏肝散可能通过降低CUMS大鼠OFC中小胶质细胞标志物Iba-1的表达,升高BDNF及其高亲和力受体TrkB及下游ERK的表达发挥治疗抑郁症作用。
Objective:To explore the protective effect and mechanism of Chaihu shugan powders on the orbitofrontal cortex(OFC)of rats with chronic unpredictable stress(CUMS)based on the theory of"Liver-Brain Related".Methods:CUMS model was established,the rats were randomly divided into normal control group,model group,escitalopram(10.5 mg/kg)positive control group and Chaihu shugan powders low(3.15 g/kg),medium(6.3 g/kg)and high(12.6 g/kg)dose groups,the normal control group and model group were given equal volume of normal saline.A small animal ultrasound imaging system was used to record the hemodynamics of the hepatic vein and portal vein;Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of OFC tissues in rats;Immunofluorescence was used to detect the expression of microglial marker Iba-1 in rat OFC tissues.The proteins expressions of BDNF,TrkB and p-ERK in OFC were detected by Western blot and the expressions of BDNF,TrkB and p-ERK mRNA in OFC were detected by Real-time PCR.Results:Compared with the model group,the blood flow velocity,flow of hepatic vein and portal vein of rats in escitalopram group and chaihu shugan powders high-dose group were significantly improved(P<0.05 or P<0.01)OFC histopathological morphology of rats in escitalopram group and Chaihu shugan powders high-dose group were obviously improved.At the same time,the production of Iba-1 in OFC of model rats in the escitalopram group and the Chaihu shugan prowders high-dose group was significantly reduced and the mRNA and protein expressions of BDNF,TrkB,p-ERK in OFC of model rats were significantly increased(P<0.05 or P<0.01).Conclusion:Chaihu shugan powders may play a role in the treatment of depression by reducing the expression of microglial marker Iba-1 in CUMS rat OFC,increasing the expressions of BDNF and its high affinity receptor TrkB and downstream ERK.
作者
张震
赵博
刘炽鉴
郭永胜
丁然
张杰
ZHANG Zhen;ZHAO Bo;LIU Chi-jian;GUO Yong-sheng;DING Ran;ZHANG Jie(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《中药材》
CAS
北大核心
2021年第7期1713-1718,共6页
Journal of Chinese Medicinal Materials
基金
国家自然科学基金项目(81560741)
贵州中医药大学博士科研启动基金([2019]27号)
关键词
柴胡疏肝散
肝脑相关
眶额叶皮层
抑郁症
小胶质细胞
Chaihu shugan powders
Liver-Brain Related
Orbitofrontal cortex
Depression
Microglia
作者简介
张震(1987-),男,博士,讲师,研究方向:抑郁症的发病机制研究,E-mail:gzzyy_zz@163.com;通讯作者:赵博,E-mail:bobtcm@126.com。
