柴郁地仙方对围绝经期抑郁症模型大鼠行为学及海马BDNF、TrkB蛋白表达的影响  

Effects of Chaiyu Dixian Recipe on Ethology and the Expressions of BDNF and TrkB in the Hippocampus of Perimenopausal Depressive Disorder Model Rats

作　　者：周静[1,2] 霍紫萱 朱红梅 王永萍[1] 李丽丽[1] 黄淑琼[1] 徐慧娴[1] ZHOU Jing;HUO Zi-xuan;ZHU Hong-mei;WANG Yong-ping;LI Li-li;HUANG Shu-qiong;XU Hui-xian(Department of Traditional Chinese Medicine,Medical College of Xiamen University,Fujian（361102)

机构地区：[1]厦门大学医学院中医系,福建361102 [2]南方医科大学中西医结合医院,广州510000

出　　处：《中国中西医结合杂志》2018年第11期1350-1355,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：福建省计生委中医药科研基金资助项目(No.wzpw201307);福建省自然科学基金计划项目(No.2017J01147)

摘　　要：目的观察柴郁地仙方对围绝经期抑郁症(perimenopausal depressive disorder, PDD)模型大鼠行为学及海马脑源性神经营养因子(brain derived neurotrophic factor, BDNF)、酪氨酸激酶B受体(tropomyosin receptor kinase B, TrkB)蛋白表达的影响,探讨其抗围绝经期抑郁症的作用机制。方法 48只3～4月龄雌性SD大鼠随机分为假手术组、模型组、阳性对照组、柴郁地仙方低、中、高剂量组,共6组,每组8只。假手术组行假手术,其余组行卵巢去势术后孤养并予以28天慢性轻度不可预见性应激(chronic unpredictable mild stress, CUMS)建立围绝经期抑郁症模型。CUMS第1天起假手术组、模型组灌服生理盐水,阳性对照组灌服盐酸氟西汀合戊酸雌二醇,中药治疗组灌服柴郁地仙方低、中、高不同浓度的汤药,其浓度分别为:0.38、0.76、1.52 g/mL,每天1次。应激过程中观察大鼠行为学及体重变化,并通过Morris水迷宫实验评价大鼠空间学习和记忆能力,应用免疫印迹法检测大鼠海马BDNF、TrkB蛋白表达情况。结果与假手术组比较,模型组大鼠体重增长缓慢,旷场实验得分及糖水偏好率均明显降低(P<0.01);Morris水迷宫空间探索时间及强迫游泳不动时间明显延长(P<0.05,P<0.01);海马BDNF、TrkB蛋白表达明显减弱(P<0.01)。与模型组比较,各治疗组大鼠的体重、行为学及Morris水迷宫空间探索时间均有不同程度变化(P<0.05,P<0.01),海马BDNF、TrkB蛋白表达量明显增加(P<0.05,P<0.01)。与阳性对照组比较,柴郁地仙方中、高剂量组的大鼠体重、行为学及海马BDNF、TrkB蛋白表达量差异无统计学意义(P>0.05)。结论柴郁地仙方可改善PDD模型大鼠行为学、体重水平及水迷宫的空间学习和记忆能力,其作用机制可能是通过提高大鼠海马中BDNF、TrkB蛋白表达量发挥的。Objective To observe the effects of Chaiyu Dixian Recipe （CDR） on ethology and the expressions of brain derived neurotrophic factor （BDNF） and tropomyosin receptor kinase B （TrkB） in the hippocampus of perimenopausal depressive disorder （PDD） model rats, and to observe its mechanism for anti-PDD. Methods A total of 48 female Sprague-Dawley rats （3 -4 months） were randomly divided into 6 groups, i.e., the sham-operation group, the model group, the positive control group, low, medium and high dose CDR groups, 8 in each group. Rats in the sham-operation group underwent sham operation. Rats in the rest groups were bred isolatedly after ovariectomy. PDD model was established by 28 days chronic unpredictable mild stress （CUMS）. Normal saline was administered to rats in the shamoperation group and the model group. Fluoxetine Hydrochloride Capsules and Estradiol Valerate were administered to rats in the positive control group. Low, medium and high dose CDR （0.38, 0.76, 1.52 g/ mL） was respectively administered to rats in each corresponding CDR group. Changes of the behavior and body weight were observed （open field test, sucrose preference, and forced swimming） during the stress process. The spatial learning and memory were evaluated by Morris water maze. The expressions of TrkB and BDNF protein in the hippocampus were detected by Western blot. Results Compared with the sham-operation group, body weight grew slowly, the scores of open field test and sucrose preference test were significantly reduced in the model group （P 〈0.01 ）. The spatial exploration time in Morris water maze and forced swimming time were significantly prolonged （P 〈0.05, P 〈0.01 ）. The expressions of hippocampal BDNF and TrkB protein were significantly attenuated （P 〈0.01 ）. Compared with the model group, body weight, ethology, space exploration time of Morris water maze varied to different degreees （P 〈0.05, P 〈0.01 ）, and the expressions of hippocampal BDNF and TrkB protein were significan

关 键 词：柴郁地仙方 围绝经期抑郁症 行为学 MORRIS水迷宫 脑源神经营养因子 酪氨酸激酶B受体 

分 类 号：R285.5[医药卫生—中药学]