Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

الملخص EN

Objectives.

The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury.

Maraviroc has been shown to have potent anti-inflammatory effects.

The aim of this study was to investigate whether PPARγ plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage.

Methods.

Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation.

During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγ inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered.

Lung water content, tissue histology, and other various parameters were measured ( n = 8 rats/group) 24 hours after resuscitation.

One-way ANOVA and Tukey’s testing were used for statistical analysis.

Results.

Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1β levels.

These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage.

Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats.

Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury.

Conclusion.

These results suggest that PPARγ might play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.