唾液酸灌胃干预肠道微生态预防小鼠更年期抑郁症的机制  

Mechanism of sialic acid intervention in intestinal microecology to prevent climacteric depression in mice

作　　者：赵平 孔令胜 季晓宇 洪波 徐艺 徐玲 张晓 陈霞 刘丽艳 常焕显 ZHAO Ping;KONG Lingsheng;JI Xiaoyu;HONG Bo;XU Yi;XU Ling;ZHANG Xiao;CHEN Xia;LIU Liyan;CHANG Huanxian(Department of Neurology,Lianyungang Oriental Hospital Affiliated to Xuzhou Medical University,Lianyungang 222042,China;不详)

机构地区：[1]徐州医科大学附属连云港东方医院神经内科,江苏连云港222042 [2]徐州医科大学附属连云港东方医院妇产科

出　　处：《山东医药》2024年第7期42-47,共6页Shandong Medical Journal

基　　金：江苏省高校重点实验室开放课题项目(XYSYSKF2021022);连云港市科技局社发项目(SF2144)。

摘　　要：目的探讨唾液酸(SA)灌胃干预肠道微生态预防小鼠更年期抑郁症的机制。方法将60只小鼠按照随机数字表法分为Sham组、模型组、SA低剂量组、SA中剂量组、SA高剂量组及盐酸氟西汀组,各10只。除Sham组外其他五组制备更年期抑郁症模型。造模成功后1~2 d,SA低、中、高剂量组分别给予16、32、64 mg/kg的SA灌胃,盐酸氟西汀组给予2 mg盐酸氟西汀灌胃,Sham组及模型组给予等体积生理盐水灌胃,每天1次,连续灌胃14 d。末次灌胃后进行强迫游泳实验(FST)、小鼠悬尾实验(TST),统计4 min内不动时间;用激光多普勒血流灌注成像仪检测肠壁血流灌注(血流灌注单位)、血流速度;16s rRNA基因测序法分析肠道菌群;Western blotting法检测肠组织糖酸结合免疫球蛋白样受体11(Siglecs)、骨钙素(OC)、组织紧密连接带蛋白1(ZO-1)、紧密连接蛋白4(claudin4)及海马组织色氨酸羟化酶2(TPH2)、酪氨酸羟化酶(TH)、吲哚胺2,3-双加氧酶(IDO)、脑源性神经营养因子(BDNF)蛋白。结果与Sham组比较,模型组TST、FST的4 min内不动时间长,血流灌注单位、血流速度、小杆菌属和小杆菌属丰度、Siglecs、OC、ZO-1、claudin4、TPH2、TH、BDNF蛋白表达低,Shannon指数、拟杆菌门和变形杆菌门丰度、IDO蛋白表达高(P均<0.05);与模型组比较,SA低、中、高剂量组及盐酸氟西汀组TST、FST短,肠壁血流灌注单位、血流速度、小杆菌属和小杆菌属丰度、Siglecs、OC、ZO-1、claudin4、TPH2、TH及BDNF蛋白表达高,Shannon指数、拟杆菌门和变形杆菌门丰度、IDO蛋白表达低(P均<0.05);SA高剂量组以上指标变化较SA低、中剂量组显著;与盐酸氟西汀组比较,SA高剂量组血流灌注单位、血流速度高(P均<0.05),两组其他指标比较差异无统计学意义(P均>0.05)。结论SA灌胃治疗小鼠更年期抑郁症的机制可能与促进小鼠肠道Siglecs高表达、降低拟杆菌门及变形杆菌丰度、促进BDNF分泌有�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 hydrochloride solution,and mice in the other groups were given equal volume of normal saline,once a day for 14 days.Forced swimming test(FST)and tail suspension test(TST)were performed after the last gavage,and the immobility time within 4 minutes was counted.The blood perfusion and blood flow velocity of the intestinal wall were detected by laser Doppler perfusion 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,Microbacillus,abundance of Microbacillus,Siglecs,OC,ZO-1,claudin4,TPH2,TH,BDNF protein expression levels were lower,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 velocity,Microbacillus,abundan

关 键 词：抑郁症 更年期 唾液酸 肠道微生态 小鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]