基于脑-肠轴探讨艾灸督脉穴对阿尔茨海默病模型小鼠认知功能及肠道菌群的影响OA

Objective To observe the effects of moxibustion at the points of governor vessel on cognitive function and gut microbiota in Alzheimer's disease(AD)model mice,and explore the mechanism of moxibustion at governor vessel in treatment of AD.Methods Eighteen APP/PS1 mice were randomly divided into a model group and a moxibustion group,with 9 mice in each group;and the other 9 C57BL/6J mice were collected as a blank group.In the moxibustion group,mild-warm moxibustion was operated at"Baihui"(GV20),suspended moxibustion was at"Fengfu"(GV16)and"Dazhui"(GV14),20 min in each intervention.Moxibustion was delivered once daily for 2 weeks.The water maze test and the novel object recognition experiment were employed to evaluate the cognitive function of mice,and the contents of β-amyloid 40(Aβ40),β-amyloid 42(Aβ42),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the hippocampus of mice were detected by ELISA,the morphology of hippocampal tissues was observed by HE staining,and the structure of fecal gut microbiota in mice was analyzed by 16S rRNA gene sequencing.The correlation of gut microbiota with the hippocampal Aβ40,Aβ42,TNF-α and IL-6 contents was analyzed.Results Compared with the blank group,in the model group,the escape latency was extended(P<0.01),the number of platform crossings decreased(P<0.01),the target quadrant residence time ratio was reduced(P<0.01);the preference index in the novel object experiment increased(P<0.001),and the discrimination coefficient decreased(P<0.001).The contents of Aβ40,Aβ42,TNF-α and IL-6 in the hippocampus rose(P<0.05),the hippocampal neuron structure was imcomplete,with irregular size and arrangement,the neurons were vacuolar and some showed pyknosis and were reduced in number.ACE,Chao1 and Shannon indexes decreased(P<0.001)and the Simpson index rose(P<0.001).The relative abundance of Proteobacteria and Deferribacteres was reduced(P<0.001),that of Lactobacillus and Pasteurella was elevated(P<0.01),while that of Alistipes decreased(P<0.01).Compared with the model group,in the moxibustion group,the escape latency was shortened(P<0.05),the number of crossing the platform increased(P<0.05),and the target quadrant residence time ratio was higher(P<0.05);the preference index decreased(P<0.001),and the discrimination coefficient increased(P<0.001).The contents of Aβ40,Aβ42,TNF-α and IL-6 in the hippocampus decreased(P<0.01).Hippocampal tissue injury was attenuated.ACE,Chao1 and Shannon indexes increased(P<0.05),and Simpson index decreased(P<0.05).The relative abundance of Proteobacteria and Deferribacteres increased(P<0.05),that of Lactobacillus decreased(P<0.001).The correlation was presented between gut microbiota and the contents of hippocampal Aβ40,Aβ42,TNF-α and IL-6 in the moxibustion group.Conclusion Moxibustion at governor vessel points can improve cognitive function in AD mice,reduce Aβ accumulation,inhibit neuroinflammation,which may be related to the recovery of gut microbiota homeostasis.