益生菌对帕金森病伴抑郁小鼠抑郁症状的改善及其肠道菌群的影响

EFFECTS OF PROBIOTICS ON DEPRESSIVE SYMPTOMS AND INTESTINAL FLORA IN MICE WITH PARKINSON ’S DISEASE AND DEPRESSION

目的 观察益生菌对帕金森病伴抑郁小鼠抑郁症状的改善及其肠道菌群的影响。方法 成年雄性小鼠(C57/BL6)50只,随机分为:正常对照组(对照组)、单纯抑郁组(抑郁组)、单纯PD组(PD组)、帕金森病伴抑郁组(PDD组)和益生菌治疗组(治疗组)。MPTP腹腔注射制作帕金森病小鼠模型,慢性不可预知温和应激建立抑郁小鼠模型。上述两种方法结合建立帕金森病伴抑郁小鼠模型。采用强迫游泳测试和糖水偏好实验检测小鼠的抑郁样行为。应用16SrDNA高通量测序分析技术分析肠道菌群特点。结果 (1)与对照组相比,抑郁组、PD组、PDD组和治疗组强迫游泳静止时间均增加、糖水偏爱率均减低,差异有统计学意义(均P<0.05);与PDD组相比,治疗组强迫游泳静止时间减少、糖水偏爱率升高,差异有统计学意义(均P<0.05)。(2)与对照组相比,抑郁组、PD组、PDD组Chao1、Observed species、Shannon、Simpson指数升高,菌群多样性较丰富(均P<0.05);与PDD组相比,治疗组Chao1、Observed species、Shannon、Simpson指数减低,菌群多样性降低(均P<0.05)。与对照组相比,PDD组肠道Firmicutes(厚壁菌门)、Bacilli(芽孢纲菌纲)和变形菌门(Proteobacteria)菌丰度降低,肠道拟杆菌门(Bacteroidetes)菌丰度增加(均P<0.05,LDA>2);与PDD组相比,益生菌治疗组,肠道Firmicutes(厚壁菌门)、Bacilli(芽孢纲菌纲)和变形菌门(Proteobacteria)菌丰度增加,拟杆菌门(Bacteroidetes)菌丰度降低(均P<0.05,LDA>2)。结论 帕金森病伴抑郁小鼠存在肠道菌群异常,益生菌可通过调节肠道菌群异常而改善帕金森病伴抑郁小鼠的抑郁症状。

Objective To observe the effect of probiotics on the improvement of depressive symptoms and intestinal flora in mice with Parkinson’s disease and depression.Methods Fifty adult male mice(C57/BL6) were randomly divided into normal control group(control group),simple depression group(depression group),simple PD group(PD group),Parkinson’s disease with depression group(PDD group) and probiotic treatment group(treatment group).The mouse model of Parkinson’s disease was made by intraperitoneal injection of MPTP,and the mouse model of depression was established by chronic unpredictable mild stress.The above two methods were combined to establish a mouse model of Parkinson’s disease with depression.The depression like behavior of mice was detected by forced swimming test and sugar water preference test.The characteristics of intestinal flora were analyzed by 16 SrDNA high-throughput sequencing.Results(1) compared with the control group, the rest time of forced swimming increased and the rate of sugar water preference decreased in the depression group, PD group, PDD group and treatment group(P< 0.05);Comparedwith PDD group, the forced swimming rest time in the treatment group decreased and the sugar water preference rate increased, the difference was statistically significant(P<0.05).(2) Compared with the control group, the indexes of Chao1,observed species, Shannon and Simpson in depression group, PD group and PDD group increased, and the diversity of flora was rich(P<0.05);Compared with PDD group, Chao1,observed species, Shannon and Simpson indexes and flora diversity decreased in the treatment group(P<0.05).Compared with the control group, the abundance of Firmicutes, bacilli and Proteobacteria decreased, and the abundance of Bacteroidetes increased in PDD group(P<0.05,LDA>2);Compared with PDD group, the abundance of Firmicutes, bacilli and Proteobacteria in the probiotic treatment group increased, and the abundance of Bacteroides decreased(P<0.05,LDA>2).Conclusion Mice with Parkinson’s disease and depression have abnormal intestinal flora, Probiotics can improve the depressive symptoms of mice with Parkinson’s disease and depression by regulating the abnormal intestinal flora.