培元解郁方对几种抑郁模型小鼠的抗抑郁作用及机制研究

目的研究培元解郁方的抗抑郁作用和作用机制。方法采用利血平2.5 mg/kg腹腔注射,建立小鼠利血平抑郁模型;采用强迫游泳方法,建立急性应激小鼠抑郁模型;采用长期(14 d)束缚加噪声,建立慢性应激小鼠抑郁模型。观察培元解郁方对利血平抑郁模型小鼠的体温、眼睑下垂、出圈率的影响;对急性应激模型、慢性应激模型小鼠的强迫游泳不动时间的影响。采用酶联免疫吸附(ELISA)法检测急性应激模型小鼠脑中5-羟色胺(5-HT)、去甲肾上腺素(NA)及吲哚胺-2,3-双加氧酶(IDO)的含量;慢性应激模型小鼠脑中5-HT、IDO的含量。并采用荧光定量PCR检测慢性应急模型小鼠脑中IDO mRNA的表达情况。结果培元解郁方各剂量组均能拮抗利血平抑郁模型小鼠的体温下降(P0.01),此外高剂量还可改善利血平引起的眼睑下垂、运动不能的状况(P0.05),中剂量组可改善运动不能的状况(P0.05)。培元解郁方中、低剂量组均可缩短急性应激模型小鼠不动时间(P0.05、P0.01),且显著增加脑中5-HT、NA的含量(P0.05、P0.01)。培元解郁方高、中、低剂量组均可不同程度地缩短慢性应激模型小鼠强迫游泳不动时间、增加脑组织中5-HT的含量、降低IDO的含量并上调IDO mRNA的表达(P0.05)。结论培元解郁方对利血平、强迫游泳、慢性应激造成的小鼠抑郁症状均有一定的改善作用。其机制可能与增加抑郁模型小鼠脑中单胺类神经递质5-HT、NA含量,抑制IDO活性、下调IDO mRNA表达有关。

Anti-depressant effect and mechanism of Peiyuan Jieyu Fang (Tonifying-original Qi Releasing-depression Formula) in several mouse models of depression

Objective To study the anti-depressant effect and mechanism of Peiyuan Jieyu Fang (Tonifying-original Qi Releasing-depression Formula).Methods The reserpine depression model was established by intraperitoneal injection of reserpine (2.5 mg/kg) in mice,acute stress depression model,by forced swimming test (FST) in mice,and chronic stress depression model,by long-term bandage (14 d) and noise in mice.The influences of Peiyuan Jieyu Fang on body temperature,ptosis and rate of overstepping bound in reserpine depression model,and on immobility time of FST in acute stress depression model and chronic stress depression model were observed.The content of brain 5-hydroxytryptamine (5-HT),noradrenalin (NA) and indoleamine-2,3-dioxygenase (IDO) in acute stress depression model,and content of 5-HT and IDO in chronic stress depression model were detected by using enzyme-linked immunosorbent assay (ELISA).The expression of IDO mRNA was detected by using fluorescence quantitative polymerase chain reaction (PCR) in chronic stress depression model.Results The decrease of body temperature was antagonized in all Peiyuan Jieyu Fang groups (abbreviated as high-dose group,mid-dose group and low-dose group) in reserpine depression model (P ＜ 0.01).The ptosis and akinesia induced by reserpine were relieved in high-dose group (P ＜ 0.05),and akinesia was relieved in low-dose group (P ＜ 0.05).The immobility time of FST was shortened (P ＜ 0.05,P ＜ 0.01),and content of 5-HT and NA were significantly increased in acute stress depression model in mid-dose group and low-dose group (P ＜0.05,P ＜0.01).The immobility time of FST was shortened in varying degrees,content of 5-HT was increased,content of IDO was decreased and IDO mRNA expression was up-regulated in chronic stress depression model in high-dose group,mid-dose group and low-dose group (P ＜ 0.05).Conclusion Peiyuan Jieyu Fang has some relief effects on depression symptoms induced by reserpine,FST and chronic stress in mice.The mechanism may be related to that Peiyuan Jieyu Fang can increase the content of 5-HT and NA,inhibit IDO activity,and down-regulate IDO mRNA expression.