中医学报2024，Vol.39Issue(7)：1357-1367,11.DOI:10.16368/j.issn.1674-8999.2024.07.226
帕宁Ⅰ号方调节肠道菌群改善PD小鼠行为学与神经递质的作用机制
Mechanism of Pa'ning Formula Ⅰ in Improving Behavior and Neurotransmitters in PD Mice by Regulating Gut Microbiota
摘要
Abstract
Objective:To explore the mechanism of Pa'ning Ⅰ Formula in improving the behavior and neurotransmitter levels of Parkin-son's disease(PD)mice based on gut microbiota.Methods:Ten mice were randomly selected as the normal group,and the remaining mice were intraperitoneally injected with MPTP(30 mg·kg-1)to establish a PD model.Fifty mice with successful modeling were ran-domly divided into model group,Madopar group,low-dose Pa'ning Formula Ⅰ group,medium-dose Pa'ning Formula Ⅰ group and high-dose Pa'ning Formula Ⅰ group,with 10 mice in each group.After the sixth injection of MPTP,the rats were given intragastric ad-ministration for 14 consecutive days,and the climbing pole test,open field test and gait analysis test were performed every 3 days.The active ingredients of Pa'ning Formula Ⅰ were identified by UPLC-HRMS,the content of dopamine(DA)in striatum was detected by ELISA,and the expression of tyrosine hydroxylase(TH)in striatum was detected by immunohistochemistry.In addition,16S rRNA high-throughput sequencing technology was used to detect the structure of gut microbiota.Results:Compared with that of the normal group,the last pole climbing time and step width of the model group were increased,while the distance and step length were decreased significantly(P<0.000 1).Compared with that of the model group,the last pole climbing time and step width were significantly de-creased,while the distance and step length were increased in the low-dose,medium-dose,and high-dose Pa'ning Formula Ⅰ groups and Madopar group significantly(P<0.000 1).The chemical components of Pa'ning Formula Ⅰ mainly include phenylalanine,3-in-dole lactic acid,vitexin,etc.Compared with that of the normal group,the content of DA in striatum of the model group was decreased significantly(P<0.000 1).Compared with that of the model group,the content of DA was increased significantly in striatum of the Pa'ning Formula Ⅰ medium-dose group,high dose group and Madopar group(P<0.000 1).It is showed in the immunohistochemistry results that the expression of TH in striatum of the model group was lower than that of the normal group significantly(P<0.000 1).Compared with that of the model group,the high-dose Pa'ning Formula Ⅰ group and Madopar group had a significant increase in the expression of TH in striatum(P<0.01).Compared with that of the normal group,the relative abundance of Turicibacter and Odoribact-er in the model group was increased,while the relative abundance of Lactobacillus,Bifidobacterium and Prevotella was decreased.Com-pared with that of the model group,the relative abundance of Prevotellaceae_Prevotella,Lactobacillus,Bifidobacterium and Prevotella in the high-dose Pa'ning Formula Ⅰ group and Madopar group was increased.The relative abundance of Staphylococcus,Turicibacter and Rikenella was positively correlated with pole climbing time significantly(P<0.05).Prevotella_Prevotella relative abundance and step length were positively correlated significantly(P<0.05);The relative abundance of Prevotella was negatively correlated with pole climbing time while positively correlated with open field distance significantly(P<0.01).The relative abundance of the Lactobacillus,Bifidobacterium are negatively correlated to the step width significantly(P<0.05).The relative abundance of Staphylococccus and Tu-ricibacter was negatively correlated with the content of DA and the expression of TH significantly(P<0.05).The relative abundance of Prevotella was positively correlated with DA content and TH expression significantly(P<0.01).The relative abundance of Lactobacil-lus was positively correlated with the expression of TH significantly(P<0.05).The relative abundance of Allobaculum was positively correlated with DA content significantly(P<0.05).Conclusion:Pa'ning Formula Ⅰ can improve the behavior and neurotransmitter level of PD mice by regulating the structure of gut microbiota,increasing the proportion of beneficial bacteria and reducing the proportion of harmful ones.关键词
帕宁Ⅰ号方/帕金森病/肠道菌群/多巴胺/酪氨酸羟化酶/小鼠Key words
Pa'ning Formula Ⅰ/Parkinson's disease/gut microbiota/dopamine/tyrosine hydroxylase/mouse分类
医药卫生引用本文复制引用
陈静文,周胜强,陈彦君,王瑞珍,万钰玲,辛凤,曾雯,刘芳..帕宁Ⅰ号方调节肠道菌群改善PD小鼠行为学与神经递质的作用机制[J].中医学报,2024,39(7):1357-1367,11.基金项目
湖南省临床医疗技术创新引导项目(2021SK51010) （2021SK51010）
湖南省中医药科研计划项目(2021083,C2022011) （2021083,C2022011）
湖南省卫生健康委员会科研计划项目(D202319019427) （D202319019427）
中国中医科学院学部委员学术传承与传播专项项目(CI2022E014XB) （CI2022E014XB）
长沙市自然科学基金项目(kq2208144) （kq2208144）
