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

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.

Quantitative proteomics reveals the effect of Yigu decoction (YGD) on protein expression in bone tissue

“…A variety of trace elements needed by the human body, such as vitamin B and cobalamin, must be absorbed through the intestine, and the absorption of cobalamin needs to be completed by binding proteins [ 39 ]. The protein digestion and absorption signaling pathway is mainly involved in the effective digestion and absorption of intestinal protein and fat [ 40 ]. Studies have shown that the effective digestion and absorption of proteins may be beneficial to cell metabolism, and high-quality cell status can help maintain immunity and functional stability in the body [ 41 ].…”

Phosphorylation‐mediated PI3K‐Art signalling pathway as a therapeutic mechanism in the hydrogen‐induced alleviation of brain injury in septic mice

“…Approximately 2%–5% of genes in the human genome encode protein kinases and phosphatases 11 . Previously, our studies demonstrated the differences in protein levels in lung tissues and intestinal tissues from septic animals and those from normal animals 12,13 …”

Evaluation of the Molecular Mechanisms of Sepsis Using Proteomics

“…In ARDS, the common intrapulmonary and extrapulmonary causes are pneumonia and sepsis, respectively (107-109). It has been shown that 2% hydrogen can effectively ameliorate multiple organ damage and increase the survival rate of sepsis mice (110)(111)(112). Bian et al ( 81) identified differentially expressed proteins, and then elucidated the molecular mechanism of H 2 in treating acute lung injury in sepsis using iTRAQ-based quantitative proteomics analysis.…”

“…In ARDS, the common intrapulmonary and extrapulmonary causes are pneumonia and sepsis, respectively ( 107 – 109 ). It has been shown that 2% hydrogen can effectively ameliorate multiple organ damage and increase the survival rate of sepsis mice ( 110 – 112 ). Bian et al.…”