Effects of adenovirus-delivered angiopoietin-1 siRNA on expression of matrix metalloproteinases in rats with acute lung injury induced by phosgene.

Daikun HE; Yiru Shao; Jie Shen; Lin Zhang; Jing Wang

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Effects of adenovirus-delivered angiopoietin-1 siRNA on expression of matrix metalloproteinases in rats with acute lung injury induced by phosgene.

Author: Daikun HE ¹ ; Yiru SHAO ¹ ; Jie SHEN ² ; Lin ZHANG ¹ ; Jing WANG ¹
Author Information

1. Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.
2. Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China. E-mail: j1999sh@163.com.
Publication Type:Journal Article
MeSH: Acute Lung Injury; chemically induced; metabolism; Adenoviridae; genetics; Angiopoietin-1; physiology; Animals; Bronchoalveolar Lavage Fluid; Chemical Warfare Agents; toxicity; Disease Models, Animal; Lung; metabolism; Matrix Metalloproteinase 2; genetics; Matrix Metalloproteinases; metabolism; Phosgene; toxicity; RNA, Messenger; genetics; RNA, Small Interfering; Rats; Tissue Inhibitor of Metalloproteinase-1; metabolism
From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2014;32(9):653-659
CountryChina
Language:Chinese
Abstract:
OBJECTIVETo 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).
METHODSWe 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.
RESULTSA 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).
CONCLUSIONAd.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.