Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats

Injury. 2012 Feb;43(2):232-6. doi: 10.1016/j.injury.2011.10.009. Epub 2011 Nov 4.

Abstract

Background and objective: Toll-like receptor 4 (TLR4) is widely recognised as a pattern recognition receptor (PRR) in the triggering of innate immunity. Lung inflammation and systemic innate immune responses are dependent on TLR4 activation undergoing pulmonary contusion. Therefore, the author investigated the effects of penehyclidine hydrochloride (PHC) on the expression of TLR4 and inflammatory responses of blunt chest trauma-induced pulmonary contusion.

Materials and methods: Male Sprague-Dawley (SD) rats were randomly assigned into three groups: normal control (NC) group, pulmonary contusion (PC) group and penehyclidine hydrochloride treatment (PHC) group. Pulmonary contusion was induced in anesthetised rats at fixed chest impact energy of 2.45J. Lung injury was assessed by the histopathology changes, arterial blood gas and myeloperoxidase (MPO) activity of lung. The serum tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of TLR4 was determined by immunohistochemistry.

Results: Blunt chest trauma produced leucocytosis in the interstitial capillaries, hypoxemia, and increased MPO activity. The expressions of TNF-α, IL-6 and TLR4 in the lung were significantly enhanced during pulmonary contusion. PHC treatments effectively attenuated pulmonary inflammation responses, as shown by improved pulmonary oxygenation, histopathology damage, decreased the MPO activity, the expressions of TNF-α, IL-6, and TLR4 after lung injury.

Conclusion: It might be concluded that PHC exhibit anti-inflammatory and protective effects in traumatic lung injury via the inhibition of the TLR4 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Contusions / immunology
  • Contusions / pathology*
  • Contusions / prevention & control
  • Enzyme-Linked Immunosorbent Assay
  • Immunity, Innate
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Lung Injury / enzymology
  • Lung Injury / immunology
  • Lung Injury / pathology*
  • Lung Injury / prevention & control*
  • Male
  • Peroxidase / metabolism
  • Protective Agents / pharmacology*
  • Quinuclidines / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Thoracic Injuries / pathology*
  • Toll-Like Receptor 4 / drug effects*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Wounds, Nonpenetrating / immunology
  • Wounds, Nonpenetrating / pathology*

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • Protective Agents
  • Quinuclidines
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • penehyclidine
  • Peroxidase