甘草黄酮的抗抑郁作用及对海马脑区神经再生的保护作用  

Antidepressant activities of flavonoids from Glycyrrhiza uralensis and its neurogenesis protective effect in rats

作　　者：樊紫周[1] 赵伟鸿[1] 果嘉[1] 程瑞凤[1] 赵金英[1] 杨卫东[1] 王英华 李巍[3] 彭晓东[1] 

机构地区：[1]宁夏医科大学基础医学院,宁夏银川750004 [2]宁夏药品检验所,宁夏银川750004 [3]日本东邦大学药学部,千叶274-8510

出　　处：《药学学报》2012年第12期1612-1617,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81060113)

摘　　要：观察宁夏地区栽培甘草(Glycyrrhiza uralensis Fisch.)中获得的甘草总黄酮提取部位(licorice flavonoids,LF)对大鼠慢性不可预见性应激抑郁模型(chronic unpredicted stress model of depression,CUS)的干预作用及对模型造成的海马齿状回(dentate gyrus,DG)颗粒细胞层下区(subgranular zone,SGZ)神经再生(neurogenesis)能力损害的保护作用,研究LF抗抑郁作用及可能的机制。通过对大鼠实施9种不同的刺激建立慢性应激抑郁模型,造模28天的同时采用不同剂量的LF(300、100和30 mg.kg-1)连续干预。采用旷场实验(open field test,OFT)、强迫游泳实验(forced swimming test,FST)和悬尾实验(tail suspension test,TST)判断LF的抗抑郁作用,放免法测定血清皮质酮含量,共聚焦显微镜对海马齿状回SGZ中5-溴脱氧尿嘧啶核苷(5'-bromo-2'-deoxyuridine,BrdU)标记的新生祖细胞(progenitor)进行分析、计数。与模型组相比,LF能够增加旷场实验中抑郁模型大鼠的直立次数、穿格数及减少粪便粒数;减少强迫游泳实验和悬尾实验中抑郁模型大鼠的不动时间;300 mg.kg-1剂量LF能降低血清皮质酮水平,同时恢复大鼠海马齿状回SGZ中BrdU标记的新生祖细胞数量。结果提示,甘草总黄酮提取部位对慢性不可预测应激引起的大鼠抑郁行为具有良好的抗抑郁药理活性,并且在较大剂量下能对应激引起的海马神经再生损害起到保护作用。Adult rats chronic unpredictable stress model of depression （CUS） was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract （licorice flavonoids, LF） from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids （300 mg·kg-1, 100 mg·kg-1 and 30 mg·kg-1） for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5＇-Bromo- 2＇-deoxyuridine （BrdU） labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids （300 mg·kg-1） can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone （SGZ） of dentate gyrus （DG） region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti- depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

关 键 词：甘草 黄酮 抑郁症 应激 神经再生 5-溴脱氧尿嘧啶核苷 

分 类 号：R285.5[医药卫生—中药学]