| Alzheimer’s disease(AD),knowing as dementia,is the most typical and common chronic neurological degenerative diseases.The main symptoms are gradual memory impairment and cognitive function obstacle.The pathological characteristics mainly for cranial nerve cells gathered a large number of beta amyloid protein plaques(senile plaque,SP),tau protein aggregate abnormal in cell and lead to neurofibrillary tangle(NFT)and inflammation,etc.The aetiological agent and mechanism of AD are complex and unclear.Amyloid cascade hypothesis,abnormal phosphorylated tau protein aggregation hypothesis and hypothesis of oxidative stress are principal hypothesis.APP/PS1 transgenic mice’ brain can produce typical pathological features which happened in AD patients.Natural polyphenols flavonoids silibinin can eliminate free radicals,inhibit free radical activity,antioxidant effect.But most silibinin was excreted with faeces because of its low bioavailability.This reason limited research about its effect position and mechanism.The number and variety of intestinal flora were huge and intestinal flora can adjust immune function,gastrointestinal development,energy metabolism and other physiological activities.The relationship between intestinal flora and host had become a hot issue.A large number of research compared patients with normal on intestinal flora structure and found that the structure of gut flora changes associated with various diseases.Based on these reasons,we assumed that silibinin can improve cognitive ability and reduce the formation of SP in the brain by regulating the structure of AD mice intestinal flora.Silibinin may have effects on prevention and treatment of AD.First stage of this study,6 months of age APP/PS1 transgenic mice and C57BL/6 mice was selected as research subjects,6 mice per group.we compared APP/PS1 mice with C57BL/6 mice on intestinal flora structure,cognition and immunohistochemical.Results showed that there were significant differences(P<0.05)in five bacteria: Rikenellaceae,Helicobacteraceae,Desulfovibrionaceae,Coriobacteriaceae and Bifidobacteriaceae.APP/PS1 mice spent longer time to find hidden platform in the behavioral experiments,poor target,and showed the typical spatial memory and cognitive disorders.By immunohistochemical analysis,there were SP in APP/PS1 mice hippocampus.Second stage of this experiment,we chose APP/PS1 transgenic mice as research subjects.16 mice were randomly divided into two groups: TgB(silibinin group)and TgBC(control group).We compared differences in intestinal flora structure,cognition and immunohistochemical between two groups after 15 days drug delivery.Analysis showed that in the top 20 of gut flora family content,there were three bacteria had significant differences(P<0.05).The content of Lachnospiraceae and Bifidobacteriaceae in TgB group were obviously higher than TgBC group,while Rikenellaceae was high in TgBC group.In behavioral experiments,mice in TgB group spent obviously shorter time to find hidden platform and they had clearer target than TgBC group.In immunohistochemical pathology analysis,all mice showed SP in hippocampus,but SP optical density of TgB group decreased than TgBC group.The results suggested that regulation of silibinin on gut flora may be one of the mechanism in AD.Final stage,two different bacteria were found: Rikenellaceae,Bifidobacteriaceae.This finding not only provided important basis to compare APP/PS1 mice with C57BL/6 mice on structure of intestinal flora,but also compared regulation of APP/PS1 mice intestinal flora by silibinin.This research expounded possible mechanism of silibinin on AD and provided scientific basis for prevention and treatment of AD. |
