title: [Early effects of ulinastatin by aerosol inhalation on rabbits with lipopolysaccharide-induced acute lung injury].
abstract: OBJECTIVE
  To study the early effects of ulinastatin (UTI) by aerosol inhalation on rabbits with acute lung injury induced by LPS, and to observe the early diagnostic value of 320-slice CT.
  
  
  METHODS
  According to the random number table, 18 specific pathogen free New Zealand white rabbits were divided into normal control group, group LPS, and group UTI, with 6 rabbits in each group. Rabbits in group LPS and group UTI were given 15 mL lipopolysaccharide (0.16 mg/mL, in the dose of 0.8 mg/kg) to reproduce acute lung injury model. Rabbits in normal control group were given equal volume of normal saline. Rabbits in UTI group were treated with UTI by aerosol inhalation for 10 min from 30 min after injury, while those in the other two groups received normal saline by aerosol inhalation. Rabbits in group LPS and group UTI were scanned by 320-slice CT at post injury hour (PIH) 6 and 24. After anesthesia, heart blood of rabbits in group LPS and group UTI was collected for determination of serum levels of TNF-α, IL-1β, and IL-6 by ELISA at PBH 24. At PBH 24, lung tissue samples were harvested for gross observation and histomorphological observation, measurement of wet to dry weight ratio, and detection of mRNA expressions of TNF-α, IL-1β, and IL-6 with RT-PCR. Above-mentioned indexes were detected in rabbits of normal control group at the same time point. Data were processed with one-way analysis of variance and LSD test.
  
  
  RESULTS
  (1) CT perfusion (CTP) image. The difference in CTP image of rabbits in group LPS between PBH 6 and PBH 24 was obvious, while that of rabbits in group UTI and normal control group was slight and not obvious respectively. (2) There were statistically significant differences in the serum levels of TNF-α, IL-1β, and IL-6 of rabbits among the three groups (with F values from 843.896 to 2 564.336, P values below 0.001). The serum levels of TNF-α, IL-1β, and IL-6 in group UTI were respectively (225 ± 9), (190 ± 8), (227 ± 6) pg/mL, and they were significantly lower than those in group LPS [(710 ± 25), (306 ± 16), (422 ± 16) pg/mL, with P values below 0.001]. (3) Gross observation. In group UTI, the degrees of pulmonary edema and pneumorrhagia of rabbits were lower than those in group LSP. (4) Histological observation. The damage to alveolar wall in group UTI was milder, and alveolar space hemorrhage and inflammatory cell infiltration were significantly less intense as compared with those in group LPS. (5) Compared with that in normal control group, the wet to dry weight ratio of lung tissue was increased in group LPS (P < 0.001). The wet to dry weight ratio of lung tissue in group UTI was significantly higher than that in normal control group but lower than that in group LPS (P values below 0.001). (6) There were statistically significant differences in mRNA levels of TNF-α, IL-1β, and IL-6 in lung tissue of rabbits among three groups (with F values from 24.700 to 69.538, P values below 0.001). The mRNA levels of TNF-α, IL-1β, and IL-6 in lung tissue of rabbits in group UTI were respectively (31.4 ± 2.7), (21.2 ± 3.3), (13.9 ± 2.4) pg/mL, which were significantly lower than those in group LPS [ (58.5 ± 10.0) , (35.1 ± 5.1), (20.7 ± 3.2) pg/mL, P values below 0.001].
  
  
  CONCLUSIONS
  UTI by aerosol inhalation can mitigate pulmonary edema and hemorrhage and inhibit inflammatory response. 320-slice CT may be used for detection of early lung injury.
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chang
authors.affiliation: Department of Burns and Plastic Surgery, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China. Email: 1922616763@qq.com.
authors.forename: Chiyu
authors.initials: C
authors.lastname: Jia
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D000336:Aerosols / Q000627:therapeutic use; D000818:Animals; D006023:Glycoproteins / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008168:Lung / Q000503:physiopathology; D055370:Lung Injury; D061330:Multidetector Computed Tomography; D009102:Multiple Organ Failure / Q000097:blood / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014361:Trypsin Inhibitors / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000336:Aerosols; D006023:Glycoproteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; C028665:urinastatin