反式虾青素对慢性应激小鼠的抗抑郁作用及其炎症相关机制

Antidepression effect and inflammatory-related mechanism of trans-astaxanthin in mice with chronic stress

目的探讨反式虾青素对慢性应激小鼠的抗抑郁作用及其炎症相关机制。方法 50只雄性ICR小鼠,随机分为对照组、模型组和反式虾青素20、40和80 mg/kg给药组,每组10只。建立小鼠慢性应激模型,应激过程共计21 d,每天1次。造模期间给药组口服相应剂量的反式虾青素,对照组和模型组给予0.5%羧甲基纤维素钠,连续给药21 d。观察强迫游泳实验和悬尾实验的小鼠不动时间,采用高效液相色谱法检测5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)和色氨酸(TRY)的含量,采用Western blot法检测小鼠海马组织和额叶皮质TNF-α和吲哚胺2,3-双加氧酶1(IDO1)蛋白的表达。结果与对照组比较,模型组小鼠强迫游泳实验和悬尾实验不动时间增加(P<0.01);与模型组比较,40 mg/kg和80 mg/kg给药组小鼠强迫游泳实验和悬尾实验不动时间减少(P<0.05)。与对照组比较,模型组海马组织和额叶皮质TNF-α和IDO1蛋白表达增加,5-HT/TRY比值降低,5-HIAA/5-HT比值升高(P<0.01);与模型组比较,40 mg/kg和80 mg/kg给药组小鼠海马组织和额叶皮质TNF-α蛋白表达减少,5-HT/TRY比值升高(P<0.05),80 mg/kg给药组小鼠海马组织和额叶皮质IDO1蛋白表达减少,5-HIAA/5-HT比值降低(P<0.05)。结论反式虾青素通过抑制海马组织和额叶皮质TNF-α表达、降低IDO1活性和增加5-HT含量,从而改善慢性应激小鼠的抑郁样症状。

Objective To investigate the antidepression effect and inflammatory-related mechanism of trans-astaxanthin in mice with chronic stress.Methods Fifty male ICR mice were randomly divided into groups of A(chronic stress+trans-astaxanthin 20 mg/kg),B(chronic stress+trans-astaxanthin 40 mg/kg),C(chronic stress+trans-astaxanthin 80 mg/kg),D(chronic stress)and E(control group).The mice models with chronic stress were established by stress process once a day for 21 days.The mice in groups of A,B and C were given trans-astaxanthin 20,40 and 80 mg/kg and those in groups of D and E were given 0.5%sodium carboxymethylcellulose for 21 days.The immobility time of mice in forced swimming experiment and suspended tail experiment was recorded.The contents of serotonin(5-HT),5-hydroxyindoleacetic acid(5-HIAA)and tryptophan(TRY)were detected by high performance liquid chromatography.The protein expressions of TNF-αand indoleamine 2,3-dioxygenase 1(IDO1)were detected in hippocampal tissues and the cortex of the frontal lobe by Western blot.Results The immobility time of mice in forced swimming experiment and suspended tail experiment was longer in group D than that in group E,which was shorter in groups of B and C than that in group D(P<0.05).The protein expressions of TNF-αand IDO1 were higher,the ratio of 5-HT to TRY was lower and the ratio of 5-HIAA to 5-HT was higher in group D than those in group E(P<0.01).Compared to group D,the protein expression of TNF-αwas lower and the ratio of 5-HT to TRY was higher in groups of B and C,and the protein expression of IDO1 and the ratio of 5-HIAA to 5-HT were lower in group C(P<0.05).Conclusion Trans-astaxanthin can improve depressive symptoms in the mice with chronic stress by inhibiting TNF-αexpression and IDO1 activity and increasing the content of 5-HT in hippocampal tissues and the cortex of the frontal lobe.