WEI Zhen,GAO Rong-jing,ZHANG Ying-yu,et al.Protective Effects of S-equol on Chronic Restraint Stress-induced Depressive-like Behavior in Mice[J].Soybean Science,2022,41(01):83-090.[doi:10.11861/j.issn.1000-9841.2022.01.0083]
雌马酚对慢性束缚致抑郁小鼠模型的改善作用及机制研究
- Title:
- Protective Effects of S-equol on Chronic Restraint Stress-induced Depressive-like Behavior in Mice
- Keywords:
- S-equol; chronic restraint stress; Hypothalamic-Pituitary-Adrenal axis; inflammatory cytokines; neurotransmitter; oxidative stress
- 文献标志码:
- A
- 摘要:
- 为探究雌马酚（S-equol，Eq）对慢性束缚抑郁模型（Chronic Restraint Stress， CRS）小鼠的改善作用，试验设空白组（Con）、模型组（CRS）、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）共5组处理。预防给药 14 d后，对模型组和雌马酚组进行28 d、10 h?d-1的慢性束缚。通过体重监测、空场、糖水偏爱和悬尾试验，研究慢性束缚应激和雌马酚对小鼠的影响；检测血清中皮质酮(CORT)，皮层中白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α( TNF-α)、去甲肾上腺素(NE)、多巴胺(DA)、超氧化物歧化酶(SOD)、丙二醛( MDA)和过氧化氢酶(CAT)水平，探究雌马酚的抗抑郁作用机制。行为学结果显示：与空白组相比，CRS模型组的自主活动能力未受到显著影响(P＞0.05)，但体重和糖水偏爱指数显著下降（P＜0.001），悬尾中的不动时间显著延长（P＜0.01）。与模型组相比，雌马酚亦未对小鼠的自主活动造成显著影响 (P＞0.05)，但显著升高小鼠的糖水偏爱指数并缩短悬尾不动时间（P＜0.05）。此外，CRS模型组小鼠血清中CORT显著上调（P＜0.001），皮层中 IL-6、IL-1β、TNF-α和MDA显著升高（P＜0.05），NE、DA、SOD和CAT水平显著降低（P＜0.05），而雌马酚预给药显著改善上述异常的指标。研究表明雌马酚可通过抑制下丘脑-垂体-肾上腺轴的过度亢进、抑制神经炎症、上调神经递质和平衡氧化应激发挥改善抑郁的作用。
- Abstract:
- To study the effects of S-equol (Eq) on chronic restraint stress (CRS)-induced depressive-like behavioral in mice and the underlying mechanisms. Mice were randomly divided into control group (Con)， CRS model group (CRS)， 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 2 weeks， the CRS group and Eq groups was conducted by continue restraint in 10 hours daily for 28 days. The effects of CRS and Eq on the mice were investigated by body weight (BW)， open field test (OFT)， sucrose preference test (SPT)， and tail suspension test (TST). In addition， corticosterone (CORT) levels in serum as well as interleukin-6 (IL-6)， interleukin-1β (IL-1β)， tumor necrosis factor α (TNF-α)， norepinephrine (NE)， dopamine (DA)， superoxide dismutase(SOD)， malondialdehyde(MDA)， and catalase (CAT) levels in cortex of mice were evaluated to explore the molecular mechanism of antidepressant effect. The results of behavioral tests showed that CRS and Eq administration were found to have no influence on the locomotor activity of mice (P＞0.05)compared to those of control group. However， the body weight and sucrose preference index of the CRS-treated mice was significantly lower than that of control mice (P＜0.001). At the same time， CRS treatment remarkably increased the immobility time of mice in TST (P＜0.01). Meanwhile， administration with Eq (10， 20 and 40 mg?kg-1) significantly elevated the sucrose consumption percent and decreased the immobility time when compared with the CRS-treated group(P＜0.05). In addition， CRS treatment significantly increased the levels of CORT in serum (P＜0.001)， decreased the contents of TNF-α， IL-6， IL-1β and MDA(P＜0.05)， and elevated the levels of NE， DA， SOD， and CAT (P＜0.05) compared to those of control mice. Eq administration significantly reversed these changes of CRS-treated mice. These findings demonstrated that Eq treatment significantly alleviated the depressive-like behavior induced by chronic restraint stress， possessing the antidepressant-like effects. The mechanisms underlying the antidepressant-like effects of Eq may be related to normalize the hypothalamic-pituitary-adrenal axis (HPA)， mediate neuroinflammation， elevate the monoamine neurotransmitter levels， and alleviate the oxidative stress.
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备注/Memo
收稿日期：2021-07-31