Effect of alprostadil on acute lung injury in septic rats

Abstract

Objective To evaluate the effect of alprostadil on acute lung injury in septic rats. Methods Thirty adult male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 3 groups (n=10 each) using a random number table: sham operation group (group S), acute lung injury group (group ALI), and alprostadil group (group Q). The animals were anesthetized with intraperitoneal 1% pentobarbital sodium 5 ml/100 g. Sepsis was induced by cecal ligation and puncture.In group Q, alprostadil (10 μg/2 ml) 2 ml/kg was injected via the tail vein at 30 min before cecal ligation and puncture.The equal volume of normal saline was given in S and ALI groups.At 24 h after operation, blood samples were taken for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations by enzyme-linked immunosorbent assay.The animals were then sacrificed.The left lungs were immediately removed for microscopic examination, and the right lungs were immediately removed for determination of wet/dry lung weight ratio (W/D ratio), and expression of TNF-α mRNA and high mobility group box-1 (HMGB1) using real-time reverse transcriptase-polymerase chain reaction. Results Compared with group S, the concentrations of serum TNF-α and IL-6 were significantly increased, and the expression of TNF-α mRNA and HMGB1 mRNA was up-regulated, and W/D ratio was increased in ALI and Q groups (P<0.05). Compared with group ALI, the concentrations of serum TNF-α and IL-6 were significantly decreased, and the expression of TNF-α mRNA and HMGB1 mRNA was down-regulated, and W/D ratio was decreased in group Q (P<0.05). The pathological changes of left lungs were significantly attenuated in group Q as compared with group ALI. Conclusion Alprostadil can reduce acute lung injury in septic rats, and the mechanism may be related to down-regulation of HMGB1 expression and inhibition of inflammatory responses. Key words: Alprostadil; Sepsis; Respiratory distress syndrome, adult; High mobility group proteins; Systemic inflammatory respones syndrome