Direct Peritoneal Resuscitation Alters Hepatic miRNA Expression after Hemorrhagic Shock

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• 作者：Jessica L. Weaver ; MD^a ; ^b ; Paul J. Matheson ; PhD^a ; ^b ; Ryan T. Hurt ; MD ; PhD^a ; Cynthia D. Downard ; MD ; MMSc ; FACS^a ; Craig J. McClain ; MD^b ; R. Neal Garrison ; MD^a ; ^b ; Jason W. Smith ; MD ; PhD ; FACS^a ; ^{jasonw.smith@louisville.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CCL ; CC motif ligand ; CR ; conventional resuscitation ; DPR ; direct peritoneal resuscitation ; HS ; hemorrhagic shock ; IL ; interleukin ; miRNA and miR ; microRNA ; mRNA ; messenger RNA ; PCR ; polymerase chain reaction
• 刊名：Journal of the American College of Surgeons
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：223
• 期：1
• 页码：68-75
• 全文大小：801 K

文摘

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.