Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury

Cell Physiol Biochem. 2017;41(5):2037-2044. doi: 10.1159/000475434. Epub 2017 Apr 14.

Abstract

Background: Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet.

Methods: In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis.

Results: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung.

Conclusions: We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients.

Keywords: Acute lung injury; Erythropoietin analogue; Inflammation; Macrophages; Traumatic brain injury.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Animals
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Erythropoietin / pharmacology*
  • Lung / metabolism*
  • Lung / pathology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Peptides / pharmacology*
  • Rats
  • Rats, Inbred Lew
  • Time Factors

Substances

  • Cytokines
  • Peptides
  • Erythropoietin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat