Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome

Abstract

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening disease with a high mortality rate, which was a common complication of fat embolism syndrome (FES). Ursodeoxycholic acid (UDCA) has been reported to exert potent anti-inflammatory effects under various conditions. In vivo, perinephric fat was injected via tail vein to establish a rat FES model, the anti-inflammatory effects of UDCA on FES-induced lung injury were investigated through histological examination, ELISA, qRT-PCR, Western blot and immunofluorescence. In vitro, human lung microvascular endothelial cells (HPMECs) were employed to understand the protective effects of UDCA. The extent of ALI/ARDS was evaluated and validated by reduced PaO2/FiO2 ratios, increased lung wet/dry (W/D) ratios and impaired alveolar-capillary barrier, up-regulation of ALI-related proteins in lung tissues (including myeloperoxidase [MPO], vascular cell adhesion molecule 1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1]), elevated protein concentration and increased proinflammatory cytokines levels (TNF-α and IL-1β) in bronchoalveolar lavage fluid (BALF). Pre-treatment with UDCA remarkably alleviated these pathologic and biochemical changes of FES-induced ALI/ARDS; our data demonstrated that pre-treatment with UDCA attenuated the pathologic and biochemical changes of FES-induced ARDS, which provided a possible preventive therapy for lung injury caused by FES.