Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury

Abstract

Objective: To ascertain if levosimendan postconditioning can alleviate lung ischemia-reperfusion injury (LIRI) in rats. Method: One hundred rats were divided into five groups: Sham (sham), ischemia-reperfusion group (I/R group), ischemic postconditioning (IPO group), levosimendan postconditioning (Levo group) and combination postconditioning group of levosimendan and 5-Hydroxydecanoic acid (Levo+5-HD group). The apoptotic index (AI) of lung tissue cells was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Expression of active cysteine aspartate specific protease-3 (active caspase-3), Bcl-2 and Bax in lung tissue was determined by immunohistochemical staining. The morphopathology of lung tissue was observed using light and electron microscopy. Results: AI values and expression of active caspase-3, Bcl-2 and Bax of lung tissue in I/R and Levo +5-HD groups were significantly higher than those in the sham group (P<0.05). AI values and expression of active caspase-3 and Bax were significantly lower, whereas that of Bcl-2 was higher significantly in the Levo group, compared with I/R and Levo+5-HD groups (P<0.05). Significant differences were not observed in comparisons between I/R and Levo +5-HD groups as well as IPO and Levo groups. Conclusion: LIRI can be alleviated by levosimendan, which simulates an IPO protective function. A postulated lung-protective mechanism of action could involve opening of mitochondrial adenosine triphosphate-sensitive potassium channels, relieving Ca2+ overload, upregulation of expression of Bcl-2, and downregulation of expression of active caspase-3 and Bax.