GAO Rong-jing,HUANG Hong,JIANG Ning,et al.Improvement Effects of Soybean Isoflavones on Lipopolysaccharide-Induced Depression-Like Behavior in Mice[J].Soybean Science,2021,40(04):539-545.[doi:10.11861/j.issn.1000-9841.2021.04.0539]
大豆异黄酮对脂多糖诱导小鼠抑郁样行为的改善作用研究
- Title:
- Improvement Effects of Soybean Isoflavones on Lipopolysaccharide-Induced Depression-Like Behavior in Mice
- Keywords:
- Soybean isoflavones; Lipopolysaccharide; Anti-depression; Inflammatory reaction; Tryptophan metabolism
- 文献标志码:
- A
- 摘要:
- 为研究大豆异黄酮对脂多糖诱导小鼠抑郁样行为的改善作用，将60只SPF级C57BL/6J雄性小鼠按体重随机分为6组，每组10只，即空白组（Control）、模型组（LPS）、SI低剂量组（10 mg·kg-1）、SI中剂量组（20 mg·kg-1）、SI高剂量组（40 mg·kg-1）和阳性药阿米替林组（10 mg·kg-1）。预防给药14 d后，首先通过空场试验观察小鼠的自主活动情况，然后采用单次腹腔注射脂多糖（1 mg·kg-1）的方法建立抑郁小鼠模型，并于LPS注射24 h后通过糖水偏爱和悬尾试验对小鼠的抑郁样行为进行评价，采用酶联免疫吸附法（ELISA）测定小鼠皮层中促炎细胞因子白介素6（IL-6）、白介素1β（IL-1β）、肿瘤坏死因子α(TNF-α)及色氨酸代谢产物犬尿氨酸(kynurenine，KYN)、5-羟色胺（5-hydroxytryptamine，5-HT）的含量。结果表明：大豆异黄酮给药后不影响小鼠的自主活动能力；与空白组相比，LPS模型组小鼠的糖水偏爱指数显著下降而悬尾不动时间显著延长，表明模型组小鼠出现抑郁样行为；与模型组相比，大豆异黄酮和阳性药阿米替林给药后显著提高小鼠的糖水偏爱指数并缩短悬尾中的不动时间，表明大豆异黄酮预防给药对LPS诱导的抑郁行为有改善作用。ELISA结果显示，与空白组相比，LPS组小鼠皮层中IL-6、IL-1β、TNF-α水平显著升高，色氨酸代谢产物5-HT水平显著降低、KYN水平显著升高，表明LPS诱导小鼠出现炎症反应且色氨酸代谢通路异常；与模型组相比，大豆异黄酮和阿米替林预给药显著改善上述异常的指标。综上表明，大豆异黄酮可通过抑制炎症反应和调节色氨酸代谢通路发挥抗抑郁作用。
- Abstract:
- The current study was conducted to explore the effects of soybean isoflavones (SI) on lipopolysaccharide (LPS)-induced depression-like behavior in mice and investigate its possible mechanisms. Sixty SPF C57BL/6J male mice were randomly divided into control group, LPS group, SI low dose group(10 mg·kg-1), SI medium dose group(20 mg·kg-1), SI high dose group(40 mg·kg-1) and positive drug (amitriptyline, 10 mg·kg-1) group, with 10 mice in each group. The depression model was established by acute intraperitoneal injection of LPS(1 mg·kg-1) once after treatment with SI for two weeks. The open field test was used to observe spontaneous activity of mice. Sucrose preference test and tail suspension test were performed to evaluate the depression behaviors of mice. The inflammatory factors (interleukin-6, interleukin-1β, and tumour necrosis factor-α), tryptophan metabolites kynurenine(KYN) and serotonin(5-HT) in the cortex of mice were measured by ELISA. The results of behavioral tests showed that SI did not affect the spontaneous activities of mice, but reversed the decrease of sucrose preference index and prolonged immobility of tail suspension induced by LPS. The results of ELISA showed that compared with control group, LPS treatment significantly increased the contents of pro-inflammatory cytokines and interrupted tryptophan metabolic pathway. However, SI administration effectively reserved these changes. The current study demonstrated that SI had the antidepressant effect, which may be related to inhibit the inflammatory responses and modulate the tryptophan metabolism.
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备注/Memo
收稿日期：2021-02-02