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J Am Coll Surg. 2020 Jan;230(1):121-129. doi: 10.1016/j.jamcollsurg.2019.09.011. Epub 2019 Oct 28.

Effect of Beta-Blockade on the Expression of Regulatory MicroRNA after Severe Trauma and Chronic Stress.

Author information

1
Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, FL.
2
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL.
3
Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, FL. Electronic address: alicia.mohr@surgery.ufl.edu.

Abstract

BACKGROUND:

Beta-blockade administration after lung contusion, hemorrhagic shock, and chronic stress has been shown to improve bone marrow function, decrease hypercatecholaminemia, and reduce inflammation. MicroRNAs (miR) are critical biologic regulators that can downregulate gene expression by causing messenger RNA degradation or inhibition of translation. This study sought to expand our understanding of the molecular mechanisms underlying the reduced inflammatory response after the administration of beta-blockade (BB) in our rodent trauma model.

STUDY DESIGN:

Male Sprague-Dawley rats aged 8 to 9 weeks were randomized to lung contusion, hemorrhagic shock with daily restraint stress (LCHS/CS) or LCHS/CS plus propranolol (LCHS/CS+BB). Restraint stress occurred 2 hours daily after LCHS. Propranolol (10 mg/kg) was given daily until day 7. Total RNA and miR were isolated from bone marrow and genome-wide miR expression patterns were assayed. Bone marrow cytokine expression was determined with quantitative polymerase chain reaction.

RESULTS:

LCHS/CS led to significantly increased bone marrow expression of interleukin (IL) 1β, tumor necrosis factor-α, IL-6, nitric oxide, and plasma C-reactive protein. There were marked differences in expression of 45 miRs in the LCHS/CS+BB group compared with the LCHS/CS group when using a p value <0.001. Rno-miR-27a and miR-25 were upregulated 7- to 8-fold in the rodents who underwent LCHS/CS+BB compared with LCHS/CS alone, and this correlated with reduced bone marrow expression of IL-1β, tumor necrosis factor-α, IL-6, nitric oxide, and reduced plasma C-reactive protein in the LCHS/CS+BB group.

CONCLUSIONS:

The genomic and miR expression patterns in bone marrow after LCHS/CS differed significantly compared with rodents that received propranolol after LCHS/CS. The use of BB after severe trauma can help mitigate persistent inflammation by upregulating Rno-miR-27a and miR-25 and reducing inflammatory cytokines in those who remain critically ill.

PMID:
31672639
PMCID:
PMC6934900
[Available on 2021-01-01]
DOI:
10.1016/j.jamcollsurg.2019.09.011

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