Effect of pretreatment with high-dose ulinastatin in preventing radiation-induced pulmonary injury in rats

In order to develop a better management strategy for radiation-induced pulmonary injury, we compared the protective effect of pretreatment and aftertreatment with different doses of ulinastatin. Two hundred and forty female Sprague–Dawley rats were randomized into five groups. Group R received radiation only, groups P1 and P2 were pretreated with different doses of i.v. ulinastatin for 3 days pre- and 4 days post-irradiation, and groups A1 and A2 were treated for 7 days post-irradiation only. Rats were sacrificed at 2 h, and at 4, 8, 16, and 24 weeks post-irradiation. The expressions of TGF-β1, TNF-α, IL-6, hydroxyproline and laminin were determined. No adverse toxicological effects of ulinastatin pretreatment were observed. Mortality and ratio of fibrotic area was lowest in group P1(5/45; 30.6 ± 3.11%, P < 0.05 vs. A2). Expressions of TGF-β1 and IL-6 in group P1 were significantly lowest at 4 weeks (3.01 ± 0.35, 549 ± 58, 32.3 ± 3.27, P < 0.01), and expressions of hydroxyproline and laminin were also lowest at 24 weeks (741 ± 68 and 82.6 ± 6.91, P < 0.01) in comparison with other groups. Significant differences were observed in expression of TGF-β1 and TNF-α in lung between group P1 and group A1 at 4 weeks (263 ± 11% vs. and 187 ± 9%, 189 ± 8% vs. 154 ± 9%, P < 0.01, P < 0.05 respectively). Pretreatment with high dose ulinastatin resulted in a milder inflammatory response and suppressed pulmonary fibrosis, which may serve as a favorable management strategy.