Resveratrol Ameliorates The Symptoms Of Parkinson's Disease Mouse And Its Effect On Gut Microbiota

BackgroundThe incidence of Parkinson's disease?PD?is increasing year by year,and clinical treatment is facing enormous challenges.More and more evidence has revealed that the gut miceobiota is involved in the occurrence and development of Parkinson's disease.Resveratrol?RV?,a traditional Chinese medicine,has many pharmacological effects such as anti-inflammatory,anti-tumor,anti-oxidation,and neuroprotection,and is a potential drug for preventing and treating Parkinson's disease.However,the effect of resveratrol in the symptoms and gut microbiota of Parkinson's disease is still unclear.ObjectiveTo investigate the effect of resveratrol on the symptoms and gut microbiota of Parkinson's disease mouse induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine?MPTP?and Probenecid?P?.Methods1.Fifty male C57BL/6 mice were randomly divided into the following five groups:control group?CK,normal diet?,resveratrol control group?RV,daily oral administration of resveratrol,30 mg/kg?,Parkinson's disease mouse model group?PD,MPTP/P induced Parkinson's disease?,resveratrol prevention and treatment group?PD_RV,daily oral administration of resveratrol on the first day of the experiment,30 mg/kg?,resveratrol treatment group?PD_RV6,daily oral administration of resveratrol started in the sixth week of the experiment,30 mg/kg?.2.Using the rotating rod test and pole test to evaluate the neurobehavioral of mice and the immunohistochemical technique to detect the pathological changes of the substantia nigra and striatum in mice.Neurobehavioral and brain tissue pathological changes were combined to assess the incidence of PD in mice and the protective and therapeutic effects of resveratrol on Parkinson's disease.3.Assessing the protective effect of resveratrol on gastrointestinal function in Parkinson's mice by measuring intestinal transit rate.4.The colon length was measured and Real-time PCR was used to quantitatively detect the abundance of inflammatory cytokines TNF-?,IL-6 and IL-1?mRNA in colonic epithelial cells,and the results were used to evaluate the effect of resveratrol in relieving intestinal inflammation in PD mice.5.The effect of resveratrol on intestinal mucosal barrier in mice with Parkinson's disease was evaluated by measuring the expression of ZO-1 protein in colon tissue and the content of serum endotoxin.6.Microbial genomic DNA were extracted from the mice feces samples at weeks 0,5,and 8 of the experiment.The abundance of total bacteria and butyrate-producing bacteria were quantitatively analyzed by Real-time PCR.The high-throughput sequencing technology was used to further detect and analyze the bacterial 16S rRNA gene diversity in the fecal samples from the 8^th week of the experiment and the gut microbiota of each groups,and to elucidate the relationship between gut microbiota and resveratrol in the prevention and treatment of Parkinson's disease.Results1.From the trend of body weight changes in mice,it can be seen that the application of MPTP,probenecid and resveratrol have no effect on the body weight of mice.2.Neurobehavioral tests showed that there were significant dyskinesias in PD mice and Immunohistochemistry results show that pathological changes in brain tissueof PD mice.Resveratrol significantly improved dyskinesia in PD mice and delayed the pathological changes of brain tissue.3.Compared with normal mice,PD mice have symptoms of intestinal dysfunction,mild colonic inflammation and increased intestinal permeability,While the intervention of resveratrol can significantly improve the above symptoms.4.High-throughput sequencing based on 16S rRNA showed that there was significant gut microbiota imbalance in PD mice:Compared with the control group mice,the abundance of Firmicutes and Deferribacteres in the chronic PD mice was significantly increased?P<0.05?,and the abundance of Bacteroidetes was significantly decreased?P<0.05?;At the Family level,the abundance of Ruminococcaceae and Deferribacteraceae in PD mice was significantly increased?P<0.05?,while Prevotellaceae was decreased?P<0.05?;At the genus level,the intestinal tract Prevotellaceae_UCG-001 was significantly decreased?P<0.05?and Oscillibacter was significantly increased?P<0.05?.The intervention of resveratrol can reverse this change to a certain extent,that is,resveratrol has a certain influence on the gut microbiota during the prevention and treatment of PD.Conclusion1.Resveratrol can effectively improve the related symptoms of Parkinson's disease mouse;2.Resveratrol has a certain effect on gut microbiota in the process of preventing and treating Parkinson's disease,which may delay the development of Parkinson's disease by increasing the abundance of butyrate-producing bacteria and Prevotellaceae.