Direct peritoneal resuscitation alters hepatic miRNA expression after hemorrhagic shock

Jessica L. Weaver, Paul J. Matheson, Ryan T Hurt, Cynthia D. Downard, Craig J. McClain, R. Neal Garrison, Jason W. Smith

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background MicroRNAs (miRNAs) are small segments of noncoding RNA that regulate gene expression and protein function, and therefore are key regulators of cellular processes including those of the inflammatory cascade after hemorrhagic shock (HS). We have previously shown that direct peritoneal resuscitation (DPR), as an adjunct to traditional IV fluid resuscitation, improves visceral blood flow and reduces pro-inflammatory cytokines released during HS. The effects of DPR on hepatic miRNA (miR) expression patterns after resuscitated HS are not known. Study Design Male Sprague-Dawley rats were divided into 3 groups: sham (no HS); conventional resuscitation (CR; HS, then resuscitated with shed blood and 2 volumes of saline); and DPR (CR plus 30 mL peritoneal dialysis solution). Animals were sacrificed at 4 hours, and miRNAs were measured using reverse transcription polymerase chain reaction. Results Use of DPR downregulated 68 of 92 hepatic miRNAs compared with only 2 of 92 upregulated when compared with CR alone, p < 0.01). Specifically, miR-9-5p, miR-122-5p, and miR-146, which regulate NFκB, were downregulated 4.1-, 3.4-, and 0.86-fold, respectively; miR-29a and miR-126 were upregulated 0.88- and 3.7-fold when DPR was compared with CR. Conclusions Adding DPR downregulated most hepatic miRNAs compared with CR alone. Some miRNAs were affected more significantly, suggesting that although this clinical intervention causes a near-global downregulation of hepatic miRNA, it still targets specific inflammatory pathways. Use of DPR for resuscitation of patients in HS may reduce hepatic inflammation to improve patient outcomes after hemorrhage.

Original languageEnglish (US)
Pages (from-to)68-75
Number of pages8
JournalJournal of the American College of Surgeons
Volume223
Issue number1
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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