[Study on effect of dexamethasone on the expression of matrix metalloproteinase and its tissue inhibitors in hyperoxia-induced lung injury].Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2004 Oct; 16(10):618-21.ZW
To observe the effect of dexamethasone on the mRNA expression of matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) in the lung tissue and to explore the protective mechanism of dexamethasone in hyperoxia-induced lung injury.
Thirty-two two-week old Wistar rats were randomly divided into atmospheric-air group (n=16) and hyperoxia group (n=16). After 7 days of continuous exposure to high concentration O (2)(>95%), the lung wet/dry(W/D) ratio, the protein content in bronchoalveolar lavage fluid(BALF) and histopathological changes of the lung were measured in 16 rats(8 in each group). The lung tissue specimens of the other 16 rats were cultured, 8 among which served as atmospheric-air control group, the remainder in the hyperoxia group were divided into hyperoxia control group,hyperoxia+dexamethasone (1 x 10(-8) mol/L) group, hyperoxia+dexamethasone (1 x 10(-6) mol/L) group, and hyperoxia+dexamethasone (1 x 10(-4) mol/L) group. Eight samples were examined in each group. After cultured for 24 hours, the lung tissue were collected and its mRNA expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined by reverse transcription-polymerase chain reaction (RT-PCR).
1. Pulmonary edema, hemorrhage and extensive inflammatory cells infiltration were observed in hyperoxia group, but no such changes were found in the atmospheric-air group. The lung W/D and the protein content in BALF in hyperoxia group were significantly higher than those in atmospheric air groups. 2. The mRNA expressions of MMP-2, MMP-9, TIMP-1, TIMP-2 and the ratio of MMP-2/TIMP-2, MMP-9/TIMP-1 were significantly higher in the hyperoxic group than those in the atmospheric-air group. 3. Dexamethasone could down-regulate the mRNA expressions of MMP-2 and MMP-9 in a concentration dependent manner. The mRNA expressions of TIMP-1, TIMP-2 also could be reduced by dexamethasone. Decreasing ratios of MMP-2/TIMP-2 and MMP-9/TIMP-1 were found in correlation with increasing concentration of dexamethasone.
Dexamethasone can reduce the mRNA expressions of MMPs as well as regulate the balance of MMPs/TIMPs, which may be one of the mechanism of its protective effect on hyperoxia-induced lung injury.