title: [Effects of adenovirus-delivered angiopoietin-1 siRNA on expression of matrix metalloproteinases in rats with acute lung injury induced by phosgene].
abstract: OBJECTIVE
  To investigate the effects of adenovirus-delivered angiopoietin-1 siRNA (Ad. Ang-1siRNA) on the expression of matrix metalloproteinase-2, 9 (MMP-2, 9) and tissue inhibitor of metallopro-teinase-1 (TIMP-1) in rats with acute lung injury (ALI) induced by phosgene (Psg).
  
  
  METHODS
  We first established a rat model of Psg-induced acute lung injury (ALI). The rats were randomly divided into 6 groups: air control group with exposure to air, air+adenovirus (air+Ad) group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after air exposure, air+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after air exposure, Psg group with exposure to 8.33 mg/L Psg (purity 100%, of the same volume as the inhaled air in the air control group) for 5 min, Psg+Ad group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after exposure to the same dose of Psg, and Psg+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after exposure to the same dose of Psg. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected 36 h after exposure. The protein expression of Ang-1, MMP-2, 9, and TIMP-1 in serum and BALF was determined by double-antibody sandwich ELISA. RT-PCR was used to determine the mRNA levels of Ang-1, MMP-2, 9, and TIMP-1 in lung tissue. The protein expression of MMP-2, 9 and TIMP-1 in lung tissue was determined by Western blot.
  
  
  RESULTS
  A rat model of Psg-induced ALI was successfully established. The levels of MMP-2, 9 in serum, BALF, and lung tissue were significantly increased in the Psg group and Psg+Ad/Ang1 group as compared with the control group (P<0.01); no significant change was observed in serum TIMP-1 protein expression (P>0.05); interestingly, TIMP-1 protein expression in BALF and lung tissue was significantly increased (P<0.01). Compared with the Psg group, the Psg+Ad/Ang1 group showed a significant decrease in MMP-2, 9 expression in BALF, serum, and lung tissue (P<0.05), but no significant change in protein expression of TIMP-1 was discovered (P>0.05).
  
  
  CONCLUSIONS
  Ad.Ang-1siRNA has a potential beneficial effect in rats with Psg-induced ALI through inhibition of MMP-2, 9 expression, but has no significant effect on the expression of TIMP-1.
authors.affiliation: Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.
authors.forename: Daikun
authors.initials: D
authors.lastname: He
authors.affiliation: Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China. E-mail: j1999sh@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000502:physiology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002619:Chemical Warfare Agents / Q000633:toxicity; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010705:Phosgene / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D002619:Chemical Warfare Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D010705:Phosgene; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2