Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Neonatal Research

Background:

• Alveolar epithelial cells (AECs) detachment and epithelial barrier dysfunction are key features of meconium aspiration syndrome (MAS).
• Previous studies indicated meconium induces AEC detachment, which is preventable by protease inhibitors.

Purpose of the Study:

• To investigate the protective effect of protease inhibitors against meconium-induced epithelial barrier dysfunction in AECs.
• To evaluate the efficacy of protease inhibitors in preventing meconium-induced lung injury in vitro and in vivo.

Main Methods:

• In vitro: Measured albumin flux across cultured human AEC monolayers (A549 cell line) exposed to meconium with or without protease inhibitors.
• In vivo: Assessed Evans Blue Dye (EBD) leakage into bronchoalveolar lavage (BAL) fluid in mice following intratracheal meconium instillation, with or without co-administered protease inhibitors.

Main Results:

• In vitro, meconium exposure significantly increased albumin flux, indicating barrier damage, but protease inhibitors blocked this effect (P<0.001).
• In vivo, meconium instillation increased EBD passage into BAL fluid, signifying vascular leakage, which was significantly reduced by protease inhibitors (P<0.01).

Conclusions:

• Protease inhibitors effectively protect alveolar epithelial cell barrier function against meconium-induced injury.
• These findings suggest a potential therapeutic role for protease inhibitors in managing meconium aspiration syndrome.