大豆黄素抗抑郁作用及其机制研究  

Antidepressive-like effect of daidzein in rats and its mechanism

作　　者：张家瑞[1] 孙达亮[1] 石娟娟[2] 赵均铭 

机构地区：[1]天津市安定医院,天津300222 [2]天津中医药大学第一附属医院,天津300193 [3]中国医学科学院血液病医院血液学研究所,天津300020

出　　处：《中国新药杂志》2015年第13期1531-1536,共6页Chinese Journal of New Drugs

摘　　要：目的:探讨异黄酮类中药单体大豆黄素对慢性不可预见性应激抑郁模型大鼠行为的影响及可能的机制。方法:将50只雄性大鼠按随机数字表法分为正常对照组(空白对照+双蒸水)、慢性不可预见性温和应激(CUMS)组(CUMS+双蒸水)、大豆黄素低剂量组D1[CUMS+大豆黄素(15 mg·kg-1·d-1)]组、大豆黄素高剂量组D2[CUMS+大豆黄素(30 mg·kg-1·d-1)]组、度洛西汀组[CUMS+度洛西汀(10 mg·kg-1·d-1)],每组10只。采用连续21 d慢性不可预见性应激造成大鼠抑郁模型,应激d 21对每组大鼠进行行为学观察,采用旷场实验、糖水偏好实验、新奇抑制摄食实验观察应激大鼠的行为学效应;采用酶联免疫吸附实验检测大鼠血清促肾上腺皮质激素、皮质酮含量;采用HE染色法观察大豆黄素对大鼠肾上腺组织形态学的影响。结果:在应激d 21,模型组大鼠水平运动得分、垂直运动得分和糖水偏好均显著低于对照组(P<0.01),大豆黄素D1,D2组(P<0.01)和度洛西汀组(P<0.05)水平运动得分、垂直运动得分和糖水偏好均显著高于模型组;大豆黄素D1组水平运动和垂直运动得分与DH组相比无统计学差异(P>0.05),但大豆黄素D2组水平运动和垂直运动得分显著高于DH组,统计具有显著性差异(P<0.01)。模型组大鼠新奇抑制摄食实验潜伏期显著高于对照组(P<0.01),大豆黄素D1,D2组(P<0.01)和度洛西汀组(P<0.05)新奇抑制摄食实验潜伏期均显著低于模型组,3组之间相比未见明显统计学差异。与对照组相比,模型组大鼠血清皮质酮和促肾上腺皮质激素浓度显著增高(P<0.01),大豆黄素D1,D2组和度洛西汀组血清皮质酮和促肾上腺皮质激素浓度均显著低于模型组(P<0.01),而上述3组之间相比未见显著差异。结论:大豆黄素对CUMS诱导的大鼠抑郁行为有显著的改善作用,其作用机制可能与抑制HPA轴功能有关。Objective： To investigate the effect of daidzein isoflavone on the behaviors of chronic unpredicted mild stress（ CUMS）-induced depression in rats and the possible underlying mechanism. Methods： Fifty male Sprague-Dawley（ SD） rats were divided into five groups. They were exposed CUMS for 21 consective days,and treated with double distilled water（ control）,daidzein（ 10 and 30 mg·kg-1per day）,or duloxetine hydrochloride（ DH,10 mg·kg-1per day）. Behaviors after CUMS protocol were assessed by open field test,sucrose intake test and novelty-suppressed feeding test（ NSFT） in all the rats. Serum adrenocorticotropic hormone（ ACTH） and corticosterone（ CORT） were detected by ELISA. The morphology of adrenal tissue were studied by HE staining. Results： Compared with the normal rats,sucrose preference,crossing and rearing were reduced in the CUMS groups（ P 〈 0. 01）,while the above indicators were increased in rats treated with daidzein（ 10 and 30 mg·kg-1,P 〈0. 01） and DH（ P 〈 0. 05） compared with CUMS control. Compared with the DH group,daidzein 10 mg·kg-1did not affect（ P 〉 0. 05）,but 30 mg·kg-1significantly increased the crossing and rearing（ P 〈 0. 01）. The CUMS rats had greater latencies to commence feeding in the NSFT than the control rats（ P 〈 0. 01）. Daidzein（ 10 and 30mg·kg-1） and DH significantly reduced the latencies compared with the CUMS control（ P 〈 0. 01 ~ 0. 05）. No significant differences were found among daidzein（ 10 and 30 mg·kg-1） and DH groups（ P 〉 0. 05）. Compared with the normal rats,the serum ACTH and CORT contents were significantly increased in the CUMS rats（ P 〈0. 01）. Daidzein（ 10 and 30 mg·kg-1） and DH markedly decreased the contents compared with the CUMS control（ P 〈 0. 01）. No significant differences were found among daidzein（ 10 and 30 mg·kg-1） and DH groups（ P 〉0. 05）. Conclusion： Daidzein has a robust antidepressant-like effect on depression-associated behaviors in

关 键 词：异黄酮类 大豆黄素 抗抑郁药 应激 HPA轴 

分 类 号：R971[医药卫生—药品]