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学科主题: 临床医学
题名:
Intestinal Alkaline Phosphatase Inhibits the Translocation of Bacteria of Gut-Origin in Mice with Peritonitis: Mechanism of Action
作者: Wang, Wei1; Chen, Shan-Wen1; Zhu, Jing1; Zuo, Shuai1; Ma, Yuan-Yuan2; Chen, Zi-Yi1; Zhang, Jun-Ling1; Chen, Guo-Wei1; Liu, Yu-Cun1; Wang, Peng-Yuan1
刊名: PLOS ONE
发表日期: 2015-05-06
DOI: 10.1371/journal.pone.0124835
卷: 10, 期:5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; CLAUDIN-2 EXPRESSION ; VEGF EXPRESSION ; INFLAMMATION ; MICROBIOTA ; COLITIS ; DISEASE ; LIPOPOLYSACCHARIDE ; PERMEABILITY ; INDUCTION
英文摘要:

Exogenous intestinal alkaline phosphatase (IAP), an enzyme produced endogenously at the brush edge of the intestinal mucosa, may mitigate the increase in aberrant intestinal permeability increased during sepsis. The aim of this study was to test the efficacy of the inhibitory effect of IAP on acute intestinal inflammation and to study the molecular mechanisms underlying IAP in ameliorating intestinal permeability. We used an in vivo imaging method to evaluate disease status and the curative effect of IAP. Two Escherichia coli (E. coli) B21 strains, carrying EGFP labeled enhanced green fluorescent protein (EGFP) and RFP labeled red fluorescent protein (RFP), were constructed as tracer bacteria and were administered orally to C57/B6N mice to generate an injection peritonitis (IP) model. The IP model was established by injecting inflammatory lavage fluid. C57/B6N mice bearing the tracer bacteria were subsequently treated with (IP+IAP group), or without IAP (IP group). IAP was administered to the mice via tail vein injections. The amount of tracer bacteria in the blood, liver, and lungs at 24 h post-injection was analyzed via flow cytometry (FCM), in vivo imaging, and Western blotting. Intestinal barrier function was measured using a flux assay with the macro-molecule fluorescein isothiocyanate dextran, molecular weight 40kD, (FD40). To elucidate the molecular mechanism underlying the effects of IAP, we examined the levels of ERK phosphorylation, and the expression levels of proteins in the ERK-SP1-VEGF and ERK-Cdx-2-Claudin-2 pathways. We observed that IAP inhibited the expression of Claudin-2, a type of cation channel-forming protein, and VEGF, a cytokine that may increase intestinal permeability by reducing the levels of dephosphorylated ERK. In conclusion, exogenous IAP shows a therapeutic effect in an injection peritonitis model. This including inhibition of bacterial translocation. Moreover, we have established an imaging methodology for live-animals can effectively evaluate intestinal permeability and aberrant bacterial translocation in IP models.

语种: 英语
所属项目编号: 201196005
项目资助者: China Health and Medical Development Foundation (Grant: Research on Surgical Infection Mechanism and Control) ; Research Fund of Peking University First Hospital
WOS记录号: WOS:000354049700051
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61927
Appears in Collections:北京大学第一临床医学院_普通外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Surg, Beijing 100871, Peoples R China
2.Peking Univ, Hosp 1, Ctr Expt Anim, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Wei,Chen, Shan-Wen,Zhu, Jing,et al. Intestinal Alkaline Phosphatase Inhibits the Translocation of Bacteria of Gut-Origin in Mice with Peritonitis: Mechanism of Action[J]. PLOS ONE,2015,10(5).
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