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      Is Open Access

      iTRAQ-Based Quantitative Proteomic Analysis of Intestines in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment

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          Abstract

          Objective

          Sepsis-associated intestinal injury has a higher morbidity and mortality in patients with sepsis, but there is still no effective treatment. Our research team has proven that inhaling 2% hydrogen gas (H 2) can effectively improve sepsis and related organ damage, but the specific molecular mechanism of its role is not clear. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis was used for studying the effect of H 2 on intestinal injury in sepsis.

          Methods

          Male C57BL/6J mice were used to prepare a sepsis model by cecal ligation and puncture (CLP). The 7-day survival rates of mice were measured. 4-kd fluorescein isothiocyanate-conjugated Dextran (FITC-dextran) blood concentration measurement, combined with hematoxylin-eosinstain (HE) staining and Western blotting, was used to study the effect of H 2 on sepsis-related intestinal damage. iTRAQ-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used for studying the proteomics associated with H 2 for the treatment of intestinal injury.

          Results

          H 2 can significantly improve the 7-day survival rates of sepsis mice. The load of blood and peritoneal lavage bacteria was increased, and H 2 treatment can significantly reduce it. CLP mice had significant intestinal damage, and inhalation of 2% hydrogen could significantly reduce this damage. All 4194 proteins were quantified, of which 199 differentially expressed proteins were associated with the positive effect of H 2 on sepsis. Functional enrichment analysis indicated that H 2 may reduce intestinal injury in septic mice through the effects of thyroid hormone synthesis and nitrogen metabolism signaling pathway. Western blot showed that H 2 was reduced by down-regulating the expressions of deleted in malignant brain tumors 1 protein (DMBT1), insulin receptor substrate 2 (IRS2), N-myc downregulated gene 1 (NDRG1) and serum amyloid A-1 protein (SAA1) intestinal damage in sepsis mice.

          Conclusion

          A total of 199 differential proteins were related with H 2 in the intestinal protection of sepsis. H 2-related differential proteins were notably enriched in the following signaling pathways, including thyroid hormone synthesis signaling pathway, nitrogen metabolism signaling pathways, digestion and absorption signaling pathways (vitamins, proteins and fats). H 2 reduced intestinal injury in septic mice by down-regulating the expressions of SAA1, NDRG1, DMBT1 and IRS2.

          Most cited references51

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          Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

          To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".
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            Severe Sepsis and Septic Shock

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              Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy.

              Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                12 November 2020
                2020
                : 14
                : 4885-4900
                Affiliations
                [1 ]Department of Anesthesiology, Tianjin Medical University General Hospital , Tianjin, People’s Republic of China
                [2 ]Tianjin Institute of Anesthesiology , Tianjin, People’s Republic of China
                [3 ]Department of Anesthesiology, Tianjin Union Medical Center , Tianjin, People’s Republic of China
                Author notes
                Correspondence: Yonghao Yu; Chao Qin Department of Anesthesiology, Tianjin Medical University General Hospital , No. 154 Anshan Road, Heping District, Tianjin300052, People’s Republic of China Email yuyonghao@126.com; qinchao0828@126.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-7140-9530
                Article
                271191
                10.2147/DDDT.S271191
                7670176
                33209018
                0e128257-926d-4002-841f-3bd284ea86a7
                © 2020 Jiang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 July 2020
                : 10 October 2020
                Page count
                Figures: 8, Tables: 3, References: 51, Pages: 16
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                sepsis,intestinal injury,hydrogen gas,proteomics,isobaric tags for relative and absolute quantitation,itraq

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