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.
Bao
Pengtao
P
Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China. bao03@163.com
Gao
Wei
W
Li
Shujun
S
Zhang
Lijiang
L
Qu
Shuoyao
S
Wu
Changgui
C
Qi
Haowen
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D055370:Lung Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009026:Mortality; D011832:Radiation Injuries / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006023:Glycoproteins; D015850:Interleukin-6; D007797:Laminin; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C028665:urinastatin; D006909:Hydroxyproline