Effect of heme oxygenase-1 protein transduction on acute lung injury in septic rats

Abstract

Objective To evaluate the effect of heme oxygenase-1 (HO-1) protein transduction on acute lung injury in septic rats. Methods Eighteen healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 210-260 g, were randomly allocated into 3 groups (n=6 each) using a random number table: sham operation group (group Sham), sepsis group (group Sep), and fusion protein PEP-1-HO-1 group (group HO). Sepsis was produced by cecal ligation and puncture (CLP). In group HO, PEP-1-HO-1 fusion protein 0.6 mg was injected via the left iliac vein at 1 h before CLP and 5 h after CLP.The equal volume of normal saline was given instead of PEP-1-HO-1 in Sham and Sep groups.At 12 h after CLP, blood samples were collected from the right common carotid artery for measurement of serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations.The rats were then sacrificed, and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method). Results Compared with group Sham, the W/D ratio and MDA content were significantly increased, the serum TNF-α and IL-6 concentrations were significantly increased (P<0.05), and the pathological changes were significantly aggravated in Sep and HO groups.Compared with group Sep, the W/D ratio and MDA content were significantly decreased, the serum TNF-α and IL-6 concentrations were significantly decreased (P<0.05), and the pathological changes were significantly attenuated in group HO. Conclusion HO-1 protein transduction can attenuate acute lung injury in septic rats, and the mechanism is probably related to inhibition of lipid peroxidation in lung tissues and systemic inflammatory responses. Key words: Heme oxygenase-1; Recombinant fusion proteins; Transduction, genetic; Sepsis; Respiratory distress syndrome, adult