Mechanism of sialic acid intervention in intestinal microecology to prevent climacteric depression in mice
Objective To investigate the mechanism of intragastric administration of sialic acid(SA)intervention in intestinal microecology to prevent climacteric depression in mice.Methods Sixty mice were randomly divided into Sham group,model group,low-dose SA group,medium-dose SA group,high-dose SA group,and fluoxetine hydrochloride group,with 10 mice in each group.Menopausal depression models were prepared in five groups except Sham group.One to two days after successful modeling,mice in the low-dose,medium-dose,and high-dose SA groups were administered 16,32 and 64 mg/kg SA solution,mice in the fluoxetine hydrochloride group were administered 2 mg fluoxetine hydrochlo-ride solution,and mice in the other groups were given equal volume of normal saline,once a day for 14 days.Forced swim-ming test(FST)and tail suspension test(TST)were performed after the last gavage,and the immobility time within 4 min-utes was counted.The blood perfusion and blood flow velocity of the intestinal wall were detected by laser Doppler perfu-sion imaging.Gut microbiota was analyzed by 16s rRNA gene sequencing.Intestinal glycoacid-binding immunoglobulin-like receptor 11(Siglecs),osteocalcin(OC),tight junction zone protein 1(ZO-1),tight junction protein 4(claudin4),and tryptophan hydroxylase 2(TPH2),tyrosine hydroxylase(TH)and indoleamine 2,3-dioxygenate in hippocampus(IDO),and brain-derived neurotrophic factor(BDNF)were detected by Western blotting.Results Compared with Sham group,the immobility time of TST and FST within 4 min was longer,blood perfusion,blood flow velocity,Microba-cillus,abundance of Microbacillus,Siglecs,OC,ZO-1,claudin4,TPH2,TH,BDNF protein expression levels were low-er,and the Shannon index,abundances of Bacteroidetes and Proteobacteria,and IDO protein expression were significantly higher in the model group(all P<0.05).Compared with the model group,the low-,medium-and high-dose SA groups and fluoxetine hydrochloride groups had shorter TST and FST,and higher intestinal wall blood perfusion,blood flow veloci-ty,Microbacillus,abundance of Microbacillus,Siglecs,OC,ZO-1,claudin4,TPH2,TH and BDNF protein expression levels,and lower Shannon index,abundances of Bacteroidetes and Proteobacteria,and IDO protein expression levels(all P<0.05).The changes of above indexes in the high-dose SA group were more significant than those of the low-dose and medium-dose SA groups.Compared with the fluoxetine hydrochloride group,blood perfusion and blood flow velocity were higher in the high-dose SA group(all P<0.05),and there were no statistically significant differences in other indexes be-tween the two groups(all P>0.05).Conclusion The mechanisms of intragastric administration of SA in the treatment of menopausal depression may be related to promoting the high expression of Siglecs in the intestinal tract of mice,reducing the abundances of Bacteroidetes and Proteobacteria,and promoting the secretion of BDNF.
万方数据
维普
