4.5 Article

Effect of siRNA against NF-κB on sepsis-induced acute lung injury in a mouse model

Journal

MOLECULAR MEDICINE REPORTS
Volume 10, Issue 2, Pages 631-637

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2014.2299

Keywords

small interfering RNA; NF-kappa B; sepsis-induced acute lung injury

Funding

  1. Beijing Municipal Commission of Education [KM200810025006]
  2. National Nature Science Foundation of China [81241071]

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The aim of the present study was to explore the protective effect of small interfering RNA (siRNA) against nuclear factor kappa B (NF-kappa B) p65 on sepsis-induced acute lung injury (ALI) in mice. In total, 70 male Kunming mice were randomly divided into a healthy control group, a sepsis group, a specific interfering group and a scrambled control group (Sc), and the latter three groups were divided into post-operational 6 and 12 h subgroups, each of which consisted of 10 mice. The mice were administered with NF-kappa B siRNA, scrambled siRNA and normal saline via tail vein injection. Following 1 h, a mouse model of septic ALI was produced by cecal ligation and puncture (CLP) in the two siRNA groups and the sepsis control group. At 6 and 12 h post-operation, the experimental mice were sacrificed and the lung tissue samples were collected. Histopathological changes, wet/dry ratio of lung weight, NF-kappa B protein and NF-kappa B p65 mRNA levels, matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were detected. Compared with the sepsis group and the Sc at the corresponding time, the expression levels of NF-kappa B p65 mRNA, the lung injury of experimental mice, the wet/dry ratio and the levels of MMP-9 mRNA and protein activity decreased, and significant differences were observed at 6 h post-operation (P<0.05). RNA interference against NF-kappa B p65 was able to decrease the expression of NF-kappa B and further inhibit the early phasic excessive inflammatory reaction in sepsis, which may alleviate ALI.

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