2022 年第 9 期 第 17 卷

益生菌对帕金森病伴抑郁小鼠5-羟色胺及相关炎性因子水平的影响

Effects of probiotics on the levels of 5-hydroxytryptamine and related inflammatory factors in mice with Parkinson′s disease and depression

作者：刘斌1李炳翰1任伯1范少凯1张艳淑2吴小坤1邓春颖1

英文作者：Liu Bin1 Li Binghan1 Ren Bo1 Fan Shaokai1 Zhang Yanshu2 Wu Xiaokun1 Deng Chunying1

单位：1华北理工大学附属医院神经内一科，唐山063000；2华北理工大学实验动物中心，唐山063000

英文单位：

关键词：益生菌；帕金森病；抑郁；5-羟色胺；炎性因子

英文关键词：Probiotics;Parkinson′sdisease;Depression;5-hydroxytryptamine;Inflammatoryfactor

• 摘要：

• 目的 观察益生菌对帕金森病伴抑郁小鼠5-羟色胺及相关炎性因子水平的影响，探讨帕金森病伴抑郁的发病机制及治疗新思路。方法  选取50只C57/BL6成年雄性小鼠，采用随机数字表法分为单纯抑郁组（抑郁组）、单纯帕金森病组（PD组）、帕金森病伴抑郁组（PDD组）、益生菌治疗组（治疗组）和正常对照组，各10只。采用1-甲基-4-苯基-1，2，3，6-四氢吡啶腹腔注射方法制备单纯帕金森病小鼠模型，慢性不可预知温和应激建立单纯抑郁小鼠模型。上述2种方法结合建立帕金森病伴抑郁小鼠模型，PDD组和治疗组小鼠均为此模型。模型制备成功后，治疗组给予益生菌灌胃，正常对照组正常饲养、不给予任何干预，抑郁组、PD组及PDD组未予药物干预。检测小鼠海马5-羟色胺水平、外周血辅助性T细胞17（Th17）细胞占比及黑质纹状体中白细胞介素17A（IL-17A）、肿瘤坏死因子α（TNF-α）及维甲酸相关核孤儿受体（ROR-γt）表达量。结果  抑郁组、PD组、PDD组和治疗组海马5-羟色胺水平均明显低于正常对照组［（97.6±3.6）、（83.7±4.2）、（79.0±3.8）、（95.2±2.0）μg/L比（114.4±4.5）μg/L］，但治疗组明显高于PDD组（均P＜0.05）。抑郁组、PD组、PDD组和治疗组小鼠外周血Th17细胞占比及黑质纹状体中IL-17A、TNF-α、ROR-γt表达量均明显高于正常对照组，但治疗组均明显低于PDD组（均P＜0.05）。结论 益生菌可升高帕金森病伴抑郁小鼠5-羟色胺水平，抑制Th17及其相关炎性因子IL-17A、TNF-α和ROR-γt的表达。

• Objective  To observe the effects of probiotics on the levels of 5-hydroxytryptamine and related inflammatory factors in mice with Parkinson′s disease and depression, and to explore the pathogenesis and treatment of Parkinson′s disease and depression. Methods  Totally 50 C57/BL6 adult male mice were randomly divided into simple depression group (depression group), simple Parkinson′s disease group (PD group), Parkinson′s disease complicated with depression group (PDD group), probiotic treatment group (treatment group) and normal control group, with 10 in each group. Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to prepare the mouse model of simple Parkinson′s disease, and the mouse model of depression was established by chronic unpredictable mild stress. The above two methods were combined to establish the mouse model of Parkinson′s disease complicated with depression, and mice in PDD group and treatment group were this model. After successful model preparation, the treatment group was given probiotics intragastric administration, the normal control group was fed normally without intervention. The depression group, PD group and PDD group were not given drug intervention. The level of 5-hydroxytryptamine in hippocampus, the rate of helper T cell (Th17) in peripheral blood, expressions of interleukin-17A (IL-17A), tumor necrosis factor-α(TNF-α) and retinoic acid related nuclear orphan receptor（ROR-γt） in substantia nigra and striatum were detected. Results  The levels of 5-hydroxytryptamine in hippocampus in depression group, PD group, PDD group and treatment group were lower than that in normal control group ［（97.6±3.6）,（83.7±4.2）,（79.0±3.8）,（95.2±2.0）μg/L vs （114.4±4.5）μg/L］, while the level in treatment group was higher than that in PDD group (all P<0.05). The rate of Th17 in peripheral blood and expressions of IL-17A, TNF-α and ROR-γt in substantia nigra and striatum in depression group, PD group, PDD group and treatment group were higher than those in normal control group and above indexes in treatment group were lower than those in PDD group (all P<0.05). Conclusion  Probiotics can increase the level of 5-hydroxytryptamine and inhibit the expressiones of Th17 and their related inflammatory factors IL-17A, TNF-α and ROR-γt in mice with Parkinson′s disease and depression.