羧甲基茯苓多糖阻遏亚慢性应激诱发的抑郁样行为

Carboxymethyl pachymaran prevented depressive behaviour induced by sub-chronic stress

探讨羧甲基茯苓多糖在缓解亚慢性应激诱发的抑郁样行为中的作用。通过连续2周温和不可预知应激,在造模的后7 d,每日分别用0.1、0.2、0.4 g/kg羧甲基茯苓多糖干预模型小鼠。采用16S rRNA高通量测序法分析小鼠肠道菌群组成,ELISA法测定血清中炎性因子水平,分别用LC-MS和GC-MS法测定粪便中神经递质和短链脂肪酸含量,并通过强迫游泳、高架十字迷宫和旷场实验测定小鼠抑郁样行为。结果表明,与模型组相比,低、中剂量的羧甲基茯苓多糖均能不同程度改善抑郁样行为,并改变肠道菌群的组成,降低革兰氏阴性菌的相对丰度(P<0.05);中剂量能够显著降低血清中IL-6 (P<0.01)和IL-2 (P<0.05)的水平;各剂量可通过调节Lactobacillus和Parabacteroides的丰度,显著下调异戊酸、NE、5-HT以及Ach的含量,从而减少IL-6的过量释放。综上,羧甲基茯苓多糖可通过调节肠道菌群组成,抑制肠源性异戊酸、NE、5-HT以及Ach的释放,降低抑郁症相关的炎性因子IL-6和IL-2的水平,从而有效阻遏亚慢性应激诱发的抑郁样行为。

The aim of the study is to investigate the protective effect of carboxymethyl pachymaran on depressive behaviour induced by sub-chronic stress.With the daily exposure to unpredictable mild stress for 2 consecutive weeks,carboxymethyl pachymaran was gavaged in mice at a daily dose of 0.1 g/kg,0.2 g/kg or 0.4 g/kg for the last 7 days of the modelling procedure.After the experiment,the composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing,and the levels of inflammatory factors in serum were determined by ELISA,the content of short-chain fatty acids in feces was measured by GC-MS,and the depressive behaviour was evaluated by open field test and elevated plus maze test and forced swim test.Compared with the model group,low and middle doses of carboxymethyl pachymaran groups improved depression-like behaviour,and changed the composition of gut microbiota with a decrease in the relative abundance of Gram-negative bacteria(P<0.05).In addition,the middle dose of carboxymethyl pachymaran could lower IL-2(P<0.05)and IL-6(P<0.01)levels in serum,and each dose of carboxymethyl pachymaran could down-regulate the levels of isovaleric acid and NE,5-HT and Ach through modulating Lactobacillus and Parabacteroides relative abundance,thereby reducing the release of IL-6.In conclusion,carboxymethyl pachymaran regulated gut microbiota composition,decreased the release of gut-derived isovaleric acid and NE,5-HT and Ach,and inhibited depression-associated inflammatory factors IL-6 and IL-2,thereby preventing depression development.