尿毒症大鼠肠道细菌移位诱发微炎性反应

・611・

.基础研究・

尿毒症大鼠肠道细菌移位诱发微炎性反应

张盼

魏萌

蒋红利

任怡

史珂慧王斐倩

【摘要】目的探讨尿毒症大鼠是否发生肠道菌群失调和肠道菌群移位以及肠道菌群移

位与微炎性反应的关系。方法建立大鼠5/6肾切除尿毒症模型及假手术模型。PCR扩增血、肝、脾、肠系膜淋巴结中细菌16SrDNA;设计血液、肝、脾中细菌特异性引物,扩增结肠内容

物、肠系膜淋巴结中细菌16SrDNA片段;焦磷酸测序分析两组大鼠回肠及结肠内容物菌群谱。

检测两组大鼠超敏C反应蛋白(hs—CRP)、白细胞介素6(IL一6)水平及肠道通透性。结果部分尿毒症大鼠个体血液、肝、脾、肠系膜淋巴结检测到细菌DNA。血液、肝、脾中细菌特异性引物可扩增相同个体肠系膜淋巴结及结肠内容物的细菌16SrDNA。尿毒症组结肠菌群谱与假手术组在目、科、属水平存在差异。尿毒症组hs—CRP、IL.6、肠道通透性均高于假手术组(均P<0.05)。结论

尿毒症大鼠肠道菌群失调,推测肠道细菌移位诱发微炎性反应。【关键词】尿毒症;

炎症;细菌移位;菌群失调

GutbacterialtranslocationcontributestomicroinflammationinexperimentaluremiaZHANG

Pan,WEIMeng,JIANGtfong-li,REN

n,SHI

Ke—hui,WANGFei—qian.Department

of

Blood

Purification,The

First

Affiliated

Hospital

ofXi’anJiaotong

University,Xi’an710061,China

Correspondingauthor:JIANGHong・li,Email:j92106@sina.con

【Abstract】

Objective

To

investigate

whether

gut

microbiome

dysbiosis

andtranslocation

occurred

in

experimental

uremia,and

whethertheyconsequentlycontributetomicroinflammation.

Methods

HealthmaleSD

rats

were

randomlydividedinto

uremicgroupandshamgroup.Uremic

groupwereoperatedfor5/6nephrectomy

to

establish

uremicmodels,while

shamgroupwereonly

operated

for

nephrocapsulotomy.Postoperative

blood,livers,spleens,andmesenteric

lymph

nodes

(MLNs)weresubjected

to

bacterial16S

ribosomalDNAamplificationtodetermine

ifbacteriawere

present.BacterialgenomicDNAsamplesfromtheMLNsandcolonwereamplifiedwithspecificprimersdesigned

by

the

16SrRNA

sequence

ofthe

species

obtainedfrom

blood,liversand

spleens.

Pyrosequencingwasusedto

analyze

theileumandcolonicmicrobiome

ofeachsubject.Intestinal

permeability

tO唧c.DTPA.plasma

hs.CRP.andIL-6weremeasured.

Results

BacterialDNAin

extraintestinalsites

andaltered

colonic

microbiomesatthe

phylum,family,andgenuslevelswere

detectedinsomeratsintheuremicgroup.BacterialgenomicDNAinMLNsandcolonwereobtainedbyprimersspecificforbacterialspeciesobservedfromblood,livers,andspleensofidenticalindividuals.Intestinal

permeability,plasma

hs-CRP,andIL-6levelswerestatisticallyhigherintheuremicgroup

comparedwiththatinshamgroup(allP<0.05).Conclusion

Gut

microbiomedysbiosis

occurs

and

presumably

bacteria

translocateto

the

systemic

and

lymph

circulation,therebycontributing

to

microinflammationinexperimentaluremia,

【Keywords】

Uremia;Inflammation;Bacterialtranslocation;Microbiomedysbiosis

研究发现,35%一50%尿毒症患者存在微炎

DOI:10.3760/cma.j.issn.1001-7097.2013.08.009基金项目:国家自然科学基金(30872457/1-10511)作者单位:710061

西安交通大学第一附属医院血液净化科

通信作者:蒋红利,Email:j92106@sina.com

性反应状态u1,微炎性反应状态与尿毒症心血管病高发生率和高病死率密切相关12,。在休克p,、严重烧伤H1、急性重症胰腺炎一1、肝硬化∞1等疾病时,

由于肠道化学屏障、机械屏障、免疫屏障受到损害,导致细菌过度生长,菌群失调,从而促使肠道菌群向血循环移位,参与并放大了炎性反应。而

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