Oxidant injury mediates TGF-β up-regulation in ventilator induced lung injury
- VernacularTitle:通气机所致肺损伤中转移生长因子β上调与氧化剂致伤的关系
- Author:
Bin OUYANG
;
Xiangdong GUAN
;
Syrkina OLGA
;
Jafari BEHROUZ
;
Juan CHEN
;
Minying CHEN
;
Lifen LI
;
A.quinn DEBORAH
- Publication Type:Journal Article
- Keywords:
respiration,artificial;
transforming growth factor beta;
oxidants;
tumor necrosis factor
- From:
Medical Journal of Chinese People's Liberation Army
2006;31(1):18-21
- CountryChina
- Language:Chinese
-
Abstract:
Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-α or H2O2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-β1 (TGF-β1 and transforming growth factor-β2 (TGF β2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-α (TNF-α) had no effects on TGF-β production in alveolar epithelial cells. Exogenous H2O2, as an oxidant, increased TGF-β production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-β production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-β in in vivo model of VILI. Conclusion TGF-β1 and TGF-β2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-β in VILI. NAC, which attenuated oxidant injury and blocked TGF-β up-regulation in VILI, could be a future therapeutic strategy in VILI.
