雌马酚(S-equol, Eq)对慢性不可预知温和刺激小鼠抑郁样行为的改善作用

Protective Effects of S-equol on Depressive-like Behavior Induced by Chronic Unpredictable Mild Stress in Mice

为探究雌马酚(S-equol, Eq)对慢性不可预知温和刺激抑郁模型(Chronic Unpredictable Mild Stress, CUMS)小鼠的改善作用,试验设空白组(Con)、模型组(CUMS)、雌马酚低剂量组(Eq-L,10 mg·kg-1)、雌马酚中剂量组(Eq-M,20 mg·kg-1)和雌马酚高剂量组(Eq-H,40 mg·kg-1),在预防给药14 d后,对模型组和雌马酚组进行CUMS造模刺激,造模42 d之后监测体重,依次进行空场、糖水偏爱、悬尾、强迫游泳和新奇抑制摄食5种行为学试验,并检测血清中皮质酮(CORT)水平。行为学结果显示:与空白组相比,CUMS模型组小鼠的自主活动能力未受到显著影响,体重和糖水偏爱指数显著下降,悬尾、强迫游泳中不动时间和新奇抑制摄食潜伏期显著延长;与模型组相比,雌马酚没有影响小鼠的自主活动,显著提高了小鼠的糖水偏爱指数,缩短了悬尾、强迫游泳不动时间和新奇抑制摄食潜伏期。此外,CUMS模型组小鼠血清中CORT显著上调,雌马酚给药显著改善上述异常指标。该结果表明雌马酚可以改善CUMS小鼠抑郁样行为,并通过抑制下丘脑-垂体-肾上腺轴的过度亢进发挥改善抑郁的作用。

In order to explore the ameliorating effects of S-equol(Eq) on depressive-like behavior induced by chronic unpredictable mild stress(CUMS), mice were randomly divided into control group(Con), CUMS model group(CUMS), Eq-Low group(Eq-L, 10 mg·kg-1), Eq-Medium group(Eq-M, 20 mg·kg-1) and Eq-High group(Eq-M, 40 mg·kg-1). After pre-administration with Eq for 14 days, the CUMS group and Eq groups were conducted by continue stress for 42 days. The antidepressant effect of Eq was investigated by body weight(BW), open field test(OFT), sucrose preference test(SPT), tail suspension test(TST), forced swimming test(FST) and novelty-suppressed feeding test(NFT). In addition, the level of corticosterone(CORT) in serum of mice was measured to explore the molecular mechanism of its antidepressant action. The results of behavioral tests showed that CUMS had no influence on the locomotor activity of mice compared to those of control group, the body weight and sucrose preference index of the CUMS-treated mice was significantly decreased, the immobility time in TST and FST and the latency time in NFT was significantly prolonged. Administration with Eq also had no influence on the locomotor activity of mice compared to the model group, while the body weight and sucrose preference index of the Eq-treated mice were significantly improved, the immobility time in TST and FST and the latency time in NFT were significantly shortened. Moreover, CUMS treatment significantly increased the levels of CORT in serum, however, Eq administration significantly reversed this change. These findings demonstrated that Eq treatment significantly alleviated the depressive-like behavior induced by CUMS, and the antidepressant-like effects of Eq may be related to normalize the hypothalamic-pituitary-adrenal axis(HPA).