Carbon Monoxide-Releasing Molecule-3 Ameliorates Acute Lung Injury in a Model of Hemorrhagic Shock and Resuscitation: Roles of p38MAPK Signaling Pathway.

Abstract

It was reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorates the HSR-induced acute lung injury (ALI); however, the specific mechanism of the protective effects against HSR-induced ALI remains unclear. To induce hemorrhagic shock, rats were bled to a mean arterial blood pressure of 30 mm Hg for 45 min and then resuscitated with shed blood via the left vein. CORM-3 (4 mg/kg or 8 mg/kg) was respectively administrated after HSR. Twelve hours post-HSR, lung injury was assessed by wet/dry (W/D) ratio, hematoxylin-eosin staining staining, and lung ultrasound; the apoptotic and pyroptotic macrophages were measured by immunofluorescence staining; and the expression of phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and total p38MAPK was measured by western blotting. SB203580 (5 mg/kg), a special inhibitor of p-p38MAPK, was administrated by abdominal cavity to assess the roles of p38MAPK in HSR-induced ALI. Increased B-line score, lung injury score, and W/D ratio indicated the fact of ALI after HSR. Twelve hours post-HSR, CORM-3 administration significantly decreased the B-line score, lung injury score, W/D ratio, apoptotic and pyroptotic macrophages, and the expressions of p-p38MAPK. Further, SB203580 not only reduced HSR-induced ALI, but also enhanced the protective effects of CORM-3 against ALI. We identified the protective effects of CORM-3 against HSR-induced ALI. The mechanism might be related to the inhibition of p38MAPK signaling pathway in lung macrophages.