硫酸亚铁对缺铁性贫血小鼠肠道健康的影响  

Effect of ferrous sulfate on intestinal health of mice with iron deficiency anemia

作　　者：楚福英 王淼 李元敬[4] 张彦龙 雷虹 冯磊[1,3] CHU Fuying;WANG Miao;LI Yuanjing;ZHANG Yanlong;LEI Hong;FENG Lei(Engineering Research Center of Agricultural Microbiology Technology,Ministry of Education,Heilongjiang University,Harbin 150500,Heilongjiang,China;Heilongjiang Key Laboratory of Ecological Restoration and Resource Utilization for Cold Region,School of Life Sciences,Heilongjiang University,Harbin 150080,Heilongjiang,China;Scientific Research Department of Heilongjiang Academy of Forestry,Harbin 150081,Heilongjiang,China;School of Materials and New Energy,Shanwei Campus,South China Normal University,Shanwei 516600,Guangdong,China)

机构地区：[1]黑龙江大学农业微生物技术教育部工程研究中心,黑龙江哈尔滨150500 [2]黑龙江大学生命科学学院/黑龙江省寒地生态修复与资源利用重点实验室,黑龙江哈尔滨150080 [3]黑龙江省林业科学院科研处,黑龙江哈尔滨150081 [4]华南师范大学汕尾校区材料与新能源学院,广东汕尾516600

出　　处：《微生物学报》2023年第2期623-637,共15页Acta Microbiologica Sinica

基　　金：黑龙江省自然科学基金(c2015023);黑龙江省森林工业总局科技计划(sgzj Y2015016);黑龙江大学横向课题(17016);“三区”科技人才项目。

摘　　要：【目的】旨在探究硫酸亚铁(FeSO_(4))对缺铁性贫血(iron deficiency anemia,IDA)小鼠肠道健康的影响。【方法】选取45只24日龄体重(16.0±1.2)g的雄性昆明小鼠,随机分成3组,每组15只,即对照组(正常饲料,饮蒸馏水)、IDA组(低铁饲料造模2周,饮去离子水)、IDA-Fe^(2+)组(造模结束后灌胃FeSO_(4)3周,饮去离子水),实验结束时采样。【结果】试验结束时,与IDA组相比,IDA-Fe^(2+)组小鼠的红细胞、血红蛋白、红细胞压积、平均红细胞体积、平均红细胞血红蛋白量、平均红细胞血红蛋白浓度等贫血指标均恢复至正常水平(P>0.05),表明FeSO_(4)具有改善IDA的功能;与对照组相比,IDA和IDA-Fe^(2+)组小鼠的氧化应激指标和肿瘤坏死因子α均显著升高(P<0.01)、紧密连接蛋白Occludin显著降低(P<0.001),IDA-Fe^(2+)组与IDA组除结肠总抗氧化能力(TAC)外均无差异显著性(P>0.05)。结肠组织HE染色结果表明:与对照组相比,IDA组小鼠的结肠组织黏膜层萎缩,黏膜层上皮细胞排列缺损,固有层萎缩。灌胃FeSO_(4)3周后,观察到IDA-Fe^(2+)组小鼠黏膜层上皮细胞排列仍有缺损,黏膜层腺泡部分存在坏死与缺损,固有层萎缩。对粪便微生物群进行的IlluminaMiSeq高通量测序结果表明,IDA会导致小鼠肠道菌群紊乱,菌群多样性指数显著改变(Shannon、Chao1、Ace和Simpson指数,P<0.05);灌胃FeSO_(4)后,相较于IDA组,IDA-Fe^(2+)组小鼠菌群多样性指数显著增加、肠道菌群的整体结构显著改善(P<0.05);在门水平上,Bacteroidetes显著降低(P<0.05),Verrucomicrobia显著升高(P<0.01),均恢复至正常水平;在属水平上,改变了主要优势菌属的丰度,有益菌Akkermansia、Coprobacter丰度显著增加(P<0.05),致病菌Parabacteroides丰度显著降低(P<0.01)。【结论】FeSO_(4)可以通过改善IDA小鼠的血液指标来缓解IDA症状,但对IDA小鼠的结肠氧化应激指标、炎症指标和结肠组织病变情况没有改善作用。补充FeSO_(4)[Objective]To explore the effect of ferrous sulfate(FeSO_(4))on the intestinal health of iron deficiency anemia(IDA)mice.[Methods]A total of 4524-day-old male Kunming mice with initial body weight of(16.0±1.2)g were randomized into 3 groups(15 in each):control group(normal diet,distilled water),IDA group(low-iron diet for 2 weeks for modeling,deionized water),and IDA-Fe^(2+)group(after modeling,gavage with FeSO_(4)for 3 weeks,deionized water).Sampling performed at the end of the experiment.[Results]Anemia indexes of mice in IDA-Fe^(2+)group,such as erythrocyte,hemoglobin,hematocrit,mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH),and mean corpuscular hemoglobin concentration(MCHC),returned to normal levels compared with those in the IDA group(P>0.05),indicating that FeSO_(4)can alleviate IDA.Compared with the control group,IDA and IDA-Fe^(2+)groups had high levels of oxidative stress indexes and tumor necrosis factorα(P<0.01)and low level of Occludin(P<0.001).The indexes,except for the total antioxidant capacity(TAC),were insignificantly different between the IDA-Fe^(2+)and IDA groups(P>0.05).As for the hematoxylin and eosin(HE)staining results of colon tissue,the IDA group showed atrophy of colonic mucosa,defective arrangement of epithelial cells in mucosa,and atrophy of lamina propria.After intragastric administration of FeSO_(4)for 3 weeks,IDA-Fe^(2+)group still demontrated defective arrangement of epithelial cells in the mucosa,necrotic and defective acini of mucosa,and atrophy of lamina propria.According to the results of Illumina MiSeq high-throughput sequencing of fecal microbiota,IDA could lead to the disorder of intestinal microflora and the variation of diversity indexes(Shannon,Chao1,Ace,and Simpson indexes)of intestinal flora(P<0.05).IDA-Fe^(2+)group showed significant increase in diversity indexes of the flora and improvement of the overall structure of intestinal flora as compared with the IDA group(P<0.05).To be specific,at the phylum level,the abudance of Bacteroidetes decreased(P<0

关 键 词：缺铁性贫血 氧化应激 肠道菌群 

分 类 号：R556.3[医药卫生—血液循环系统疾病]