百合地黄汤对抑郁症大鼠肠道菌群的影响

目的：探究百合地黄汤对抑郁症大鼠肠道菌群的影响。方法：采用孤养和慢性不可预知性温和应激刺激制备大鼠抑郁症模型，经百合地黄汤给药后，采用糖水偏好试验和旷场试验进行药效学评价，并对大鼠的结肠进行病理学检测；收集大鼠粪便，应用16S rRNA高通量测序技术对大鼠肠道菌群多样性进行分析，并进行功能预测。结果：与正常组比较，模型组大鼠体质量明显降低；给药后，各剂量组大鼠体质量均有增加的趋势。糖水偏好实验结果显示，与正常组比较，模型组大鼠糖水偏爱度明显减弱（P<0.01）；给药后，各剂量组糖水偏爱度均有增强的趋势，且中剂量组和低剂量组差异有统计学意义（P<0.01）。在旷场实验中，与正常组比较，模型组大鼠自主活动显著减弱（P<0.01）；给药后，各剂量组大鼠自主活动均有增强的趋势，且低剂量组与模型组比较差异有统计学意义（P<0.05）。病理结果显示，模型组大鼠结肠黏膜遭到破坏，经百合地黄汤给药后，各给药组结肠黏膜损伤均有不同程度的恢复。在菌群多样性方面，经百合地黄汤治疗后，在门水平上，厚壁菌门的丰度明显增加，拟杆菌门、疣微菌门、变形菌门及蓝藻门的丰度明显降低，其中变形菌门和蓝藻门改变具有统计学意义（P<0.05）。在属水平上，降低了norank_f__Muribaculaceae、瘤胃球菌属及粪球菌属等菌属的丰度，升高了乳酸菌属、罗姆布茨菌属、Turicibacter及芽孢杆菌属等菌属的丰度，其中norank_f__Muribaculaceae、罗姆布茨菌属、Turicibacter、norank_f__Eubacterium_coprostanoligenes_group、Prevotellaceae_UCG-001及Prevotellaceae_UCG-001的改变有统计学意义（P<0.05）。京都基因和基因组百科全书(KEGG)功能预测显示，差异菌群的功能与氨基酸代谢、能量代谢、神经系统以及神经退行性疾病等相关。结论：百合地黄汤能够调节抑郁症大鼠的肠道菌群进而改善抑郁症大鼠的抑郁样行为。

Effects of Baihe Dihuang Decoction on Intestinal Flora of Depressed Rats

To explore the effect of Baihe Dihuang Decoction on the behavior and intestinal flora of depressed rats.Methods:The rat model of depression was prepared by solitary feeding and chronic unpredictable mild stress stimulation.After administration of Baihe Dihuang Decoction，the pharmacodynamics were evaluated by sugar water preference test and open field test，and the colonic pathology of rats was examined.Meanwhile，rat feces were collected，and 16S rRNA high-throughput sequencing technology was used to analyze the diversity of rat intestinal flora and predict its function.Results:Compared to the normal group，the weight of rats in the model group decreased significantly.After administration，the weight of rats in each dose group had a tendency to increase.The results of sugar water preference experiment showed that the sugar water preference of rats in the model group was significantly weakened compared to the normal group(P<0.01).After administration，the preference for sugar water in all dose groups increased，and the difference between medium dose group and low dose group was statistically significant(P<0.01).In an open field experiment，compared to the normal group，the autonomic activity of rats in the model group significantly decreased(P<0.01).After administration，the autonomous activity of rats in all dose groups had a trend of enhancement，and the difference between the low-dose group and the model group was statistically significant(P<0.05).The pathological results showed that the colonic mucosa of the model group was destroyed，and the colonic mucosa of each administration group recovered to different degrees after receiving Baihe Dihuang Decoction.In terms of bacterial diversity，after treatment with Baihe Dihuang Decoction，the abundance of Firmicutes increased，and the abundance of Bacteroidota，Verrucomicrobia，Proteobacteria and Cyanobacteria decreased.The changes of Proteobacteria and Cyanobacteria were statistically significant(P<0.05).At the genus level，the abundances of genera such as norank_f__Muribaculaceae，Ruminococcus and Faecalibacterium decreased，and the abundance of genera such as Lactobacillus，Rombutzia，Turicibacter and Bacillus increased.The changes in norank_f__Muribaculaceae，Rombutzia，Turicibacter，norank_f__Eubacterium_coprostanoligenes_group，Prevotellaceae_UCG-001 and Prevotellaceae_UCG-001 were statistically significant(P<0.05).KEGG function prediction showed that the function of different flora was related to amino acid metabolism，energy metabolism，nervous system and neurodegenerative diseases.Conclusion:Baihe Dihuang Decoction can improve the depression-like behavior of depressed rats by regulating the intestinal flora of depressed rats.