Role of mitochondrial fusion-fission in endotoxin-induced acute lung injury in rats

Abstract

Objective To evaluate the role of mitochondrial fusion-fission in endotoxin-induced acute lung injury in rats. Methods Twenty healthy male Sprague-Dawley rats, weighing 160-180 g, were equally and randomly divided into either control group (group C) or endotoxin-induced acute lung injury group (group L) using a random number table. Lipopolysaccharide 5 mg/kg was injected intravenously in group L, while the equal volume of normal saline 0.5 ml was given instead in group C. The animals were sacrificed at 6 h after administration of lipopolysaccharide or normal saline. The lungs were immediately removed for measurement of wet to dry lung weight ratio (W/D ratio) , superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The mitochondrial fusion proteins mitofusin 1 (Mfn1) , Mfn2 and optic atrophy 1 (OPA1) mRNA and protein expression was detected, and mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis1) mRNA and protein expression was also detected in lung tissues. Results Compared to group C, the W/D ratio and MDA contents in lung tissues were significantly increased, SOD activity was decreased, Mfn1, Mfn2 and OPA1 mRNA and protein expression in lung tissues was down-regulated, and Drp1 and Fis1 mRNA and protein expression was up-regulated in group L. The pathological damage to lung tissues was obviously aggravated in group L when compared to group C. Conclusion The mechanism underlying endotoxin-induced acute lung injury is related to enhanced oxidative stress responses caused by decreased mitochondrial fusion and increased mitochondrial fission in rats. Key words: Mitochondrial proteins; Respiratory distress syndrome, adult; Endotoxemia; Mitochondrial fusion; Mitochondrial fission