海参磷脂通过调节TRP-KYN途径改善慢性应激诱导斑马鱼抑郁样行为

Sea Cucumber Phospholipids Improve Chronic Stress Induced Depression-Like Behavior in Zebrafish by Regulating TRP-KYN Pathway

摘要:

为了探究海参磷脂对慢性不可预知性应激（Chronic Unpredictable Mild Stress, CUMS）诱导斑马鱼产生抑郁样行为的影响及机制，将斑马鱼随机分为对照组、应激组、应激+低剂量（50 mg/kg）、应激+高剂量（100 mg/kg）海参磷脂干预组。应激结束后进行新型水箱和明暗箱行为测试，采用酶联免疫吸附试验（Enzyme Linked Immunosorbent Assay, ELISA）测定脑中白细胞介素（Interleukin, IL）-10、IL-6、吲哚胺2,3-双加氧酶（Indoleamine-2,3-Dioxygenase, IDO）、色氨酸（Tryptophan, TRP）、犬尿氨酸（Kynurenine, KYN）含量变化，高效液相色谱（High Performance Liquid Chromatography, HPLC）检测五羟色胺（5-Hydroxytryptamine, 5-HT）水平。与应激组相比，低（50 mg/kg）、高剂量（100 mg/kg）海参磷脂组斑马鱼在新型水箱和明暗箱行为测试中抑郁程度均有效减轻，脑中IL-10含量分别增加12.05%和15.26%（P<0.05和P<0.01），IL-6含量分别减少12.23%和14.87%（P<0.01和P<0.000 1），IDO活性分别降低14.12%和22.20%（P<0.01和P<0.000 1），TRP含量分别增加4.07%和4.33%（P<0.05），KYN含量分别减少6.83%和8.67%（P<0.05），KYN/TRP比值分别降低9.43%和11.32%（P<0.05），5-HT含量增加28.57%（P<0.05）。因此，海参磷脂具有改善抑郁的作用，其机制可能是通过改善炎症及IDO激活的TRP-KYN通路引起的5-HT的合成减少。该研究可为海参磷脂在抗抑郁功能的产品研发提供新思路。

Abstract:

The effect and mechanism of sea cucumber phospholipids on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in zebrafish were investigated. Zebrafish were randomly divided into control group, stress group, stress + low dose (50 mg/kg), stress + high dose (100 mg/kg) sea cucumber phospholipid intervention group. Then, the novel tank and light-dark box behavior tests were performed, the contents of interleukin (IL)-10, IL-6, indoleamine-2,3-dioxygenase (IDO), Tryptophan (TRP) and Kynurenine (KYN) were determined by enzyme linked immunosorbent assay (ELISA) and the level of 5-hydroxytryptamine (5-HT) was detected by high performance liquid chromatography (HPLC). Compared with the stress group, the depression degree of zebrafish in the low (50 mg/kg) and high dose (100 mg/kg) sea cucumber phospholipid groups was effectively alleviated in the new tank and the light-dark box behavior test. The contents of IL-10 in the brain were increased by 12.05 % and 15.26% (P<0.05 and P<0.01), the contents of IL-6 were decreased by 12.23% and 14.87% (P<0.01 and P<0.000 1), the activities of IDO were decreased by 14.12% and 22.20% (P<0.01 and P<0.000 1), and the contents of TRP were increased by 4.07% and 4.33% (P<0.05), the contents of KYN were decreased by 6.83% and 8.67% (P<0.05), the ratios of KYN/TRP were decreased by 9.43% and 11.32% (P<0.05) respectively, and the contents of 5-HT were increased by 28.57% (P<0.05). Therefore, depression can be improved by sea cucumber phospholipids. The mechanism might be realized by improving inflammation and the reduction of 5-HT synthesis caused by the TRP-KYN pathway activated by IDO, which could provide new ideas for the product development of sea cucumber phospholipids in antidepressant function.