Dataset Information

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

ABSTRACT:

Background/aims

The aim of present study was to assess the protective effects of Shenfu injection (SI) on the intestinal mucosa and its regulation on the mucosal immune responses in rats with sepsis.

Materials and methods

Sprague-Dawley rats were randomly divided into the sham, model, low-dose SI (LSF), and high-dose SI (HSF) groups. Sham animals underwent laparotomy only, whereas sepsis was modeled by cecal ligation and puncture in the remaining groups. At 2 h post-surgery, the LSF and HSF groups were intraperitoneally administered 5 and 20 mL/kg SI, respectively, whereas other animals with saline. At 12 h and 24 h post-surgery, eight rats per group were sacrificed, and blood and intestinal tissues were collected. The intestinal mucosa was analyzed by hematoxylin and eosin staining. Serum tumor necrosis factor (TNF)-? and interleukin (IL)-6 concentrations, as well as secretory immunoglobulin A (sIgA) content in the intestinal mucosa, were evaluated by enzyme-linked immunosorbent assay. CD3 and ??T lymphocytes were quantified by flow cytometry. Animal survival until 72 h was also recorded.

Results

Intestinal mucosal injury was significantly higher in model animals than in sham animals at postoperative 12 h and 24 h. Serum TNF-? and IL-6 levels were markedly increased, whereas sIgA and CD3 and ??T cell amounts were overtly decreased (p<0.01). The LSF and HSF rats showed lower mortality, intestinal mucosal injury, and serum TNF-? and IL-6 levels (p<0.05), as well as higher sIgA levels and CD3 and ??T cell amounts, than the model group (p<0.01), with a dose-dependent manner.

Conclusion

SI dose-dependently prolongs survival and protects the intestinal mucosa in rats with sepsis, possibly through strengthening innate immunity instead of acquired immunity.

SUBMITTER: Jin S

PROVIDER: S-EPMC6453654 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

Jin Shuifang S Jiang Ronglin R Lei Shu S Jin Liming L Zhu Chen C Feng Wen W Shen Yingying Y

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 20190401 4

<h4>Background/aims</h4>The aim of present study was to assess the protective effects of Shenfu injection (SI) on the intestinal mucosa and its regulation on the mucosal immune responses in rats with sepsis.<h4>Materials and methods</h4>Sprague-Dawley rats were randomly divided into the sham, model, low-dose SI (LSF), and high-dose SI (HSF) groups. Sham animals underwent laparotomy only, whereas sepsis was modeled by cecal ligation and puncture in the remaining groups. At 2 h post-surgery, the L ...[more]

PMID: 30666971

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Project description:Sepsis remains a leading cause of death and currently has no pathogenesis-specific therapy. Hampered progress is partly due to the lack of insight into deep mechanistic processes. Deciphering the functions of microRNAs in sepsis pathogeny became a dynamic research topic in the last decade. To screen for new microRNA targets for sepsis therapeutics, we used human samples: microRNA array data from peripheral blood mononuclear cells (PBMCs) from sepsis patients and controls, whole blood samples from sepsis survivors; and multiple animal models: mouse cecum ligation-puncture (CLP)-induced sepsis, mouse viral microRNA challenge, and baboon Gram-positive and Gram-negative sepsis models. miR-93-5p met the criteria for a therapeutic target, being overexpressed in baboons which died early after induction of sepsis and downregulated in humans who survived after sepsis. Therapeutically, inhibiting miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in old mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially CD4+ subset. Ago2-immunoprecipitation in miR-93-knockout T cells identified important regulatory receptors, CD28 and CD160, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis in the elderly through its regulation of both innate and adaptive immunity. We applied the Ago2-RIP Chip (Ribonucleoprotein ImmunoPrecipitation followed by microarray analysis) to identify miR-93-5p target mRNAs. This methodology uses beads coupled to either anti-Ago2 antibody (or an IgG control) to pull down the RISC complex together with any miRNA-interacting mRNAs. To define target genes of miR-93-5p, we assessed mRNA transcripts enriched in the Ago2-IP fraction of JURKAT parental cells or control cells (where miR-93-5p is present) but not in the two KO clones (where miR-93-5p is absent) by microarray

Dataset Information

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

Background/aims

Materials and methods

Results

Conclusion

Publications

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

Similar Datasets

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