Ischemia-reperfusion (IR) injury is a severe complication in lung transplantation characterized by inflammation, alveolar damage, and hypoxemia. Alpha 1-antitrypsin (A1AT), a protease inhibitor, is currently used clinically for the treatment of A1AT deficiency emphysema. A1AT has been shown to have the potential to reduce IR injury through its anti-inflammatory and anti-apoptotic effects. We hypothesized that A1AT will ameliorate IR injury through these effects. We tested A1AT in two models of IR: a cell culture model of simulated lung transplantation and a rat in situ pulmonary ligation model. In cell culture, we found that A1AT exerts its protective effects by inhibiting cell death and inflammatory cytokine release in a dose-dependent manner. In the rat pulmonary ischemia-reperfusion model, we found that A1AT improved lung function by inhibiting apoptosis and inflammation. There is potential for future application of A1AT in the treatment of IR injury in lung transplantation.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33210 |
| Date | 20 November 2012 |
| Creators | Gao, Wenxi |
| Contributors | Liu, Mingyao |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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