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-beta1, TNF-alpha, 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-beta1 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-beta1 and TNF-alpha 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.