Weaver Jessica L, Matheson Paul J, Hurt Ryan T, Downard Cynthia D, McClain Craig J, Garrison R Neal, Smith Jason W
Department of Surgery, University of Louisville, Louisville, KY; Robley Rex Veterans Affairs Medical Center, Louisville, KY.
Department of Surgery, University of Louisville, Louisville, KY.
J Am Coll Surg. 2016 Jul;223(1):68-75. doi: 10.1016/j.jamcollsurg.2016.03.024. Epub 2016 Mar 26.
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.
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.
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.
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.
微小RNA（miRNA）是一类非编码RNA小片段，可调节基因表达和蛋白质功能，因此是细胞过程的关键调节因子，包括失血性休克（HS）后的炎症级联反应。我们之前已经表明，直接腹腔复苏（DPR）作为传统静脉液体复苏的辅助手段，可改善内脏血流并减少HS期间释放的促炎细胞因子。DPR对复苏后HS肝脏miRNA（miR）表达模式的影响尚不清楚。
将雄性Sprague-Dawley大鼠分为3组：假手术组（无HS）；传统复苏组（CR；HS，然后用失血和2倍体积的生理盐水进行复苏）；和DPR组（CR加30 mL腹膜透析液）。在4小时时处死动物，使用逆转录聚合酶链反应测量miRNA。
与单独的CR相比，使用DPR使92种肝脏miRNA中的68种下调，而单独CR时92种中仅2种上调（p <0.01）。具体而言，调节NFκB的miR-9-5p、miR-122-5p和miR-146分别下调4.1倍、3.4倍和0.86倍；与CR相比，DPR时miR-29a和miR-126分别上调0.88倍和3.7倍。
与单独的CR相比，添加DPR可使大多数肝脏miRNA下调。一些miRNA受到的影响更显著，这表明尽管这种临床干预导致肝脏miRNA几乎全面下调，但它仍然针对特定的炎症途径。使用DPR对HS患者进行复苏可能会减轻肝脏炎症，以改善出血后患者的预后。
