부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1440-1681.2006.04440.x Byline: Hong-Wei Yao (*), Lian-Gen Mao ([dagger]), Jian-Ping Zhu (*) Keywords: acute lung injury; lipopolysaccharide; pravastatin Abstract: SUMMARY The present study was designed to determine whether pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in BALB/c mice. Acute lung injury was induced successfully by intratracheal administraiton of LPS (3 mg/g) in BALB/c mice. Pravastatin (3, 10 and 30 mg/kg, i.p.) was administered to mice 24 h prior to and then again concomitant with LPS exposure. Challenge with LPS alone produced a significant increase in lung index and the wet/dry weight ratio compared with control animals. Pulmonary microvascular leakage, as indicated by albumin content in the bronchoalveolar lavage fluid (BALF) and extravasation of Evans blue dye albumin into lung tissue, was apparently increased in LPS-exposed mice. Lipopolysaccharide exposure also produced a significant lung inflammatory response, reflected by myeloperoxidase activity and inflammatory cell counts in BALF. Furthermore, histological examination showed that mice exposed to LPS also exhibited prominent inflammatory cell infiltration and occasional alveolar haemorrhage. Pravastatin (3, 10 or 30 mg/kg, i.p.) produced a significant reduction in multiple indices of LPS-induced pulmonary vascular leak and inflammatory cell infiltration into lung tissue. Elevated tumour necrosis factor (TNF)-a levels in lung tissue homogenates of ALI mice were significantly decreased after administration of 10 or 30 mg/kg pravastatin. These findings confirm significant protection by pravastatin against LPS-induced lung vascular leak and inflammation and implicate a potential role for statins in the management of ALI. The inhibitory effect of pravastatin was associated with its effect in decreasing TNF-a. Author Affiliation: (*)Zhejiang Respiratory Drugs Research Laboratory of State Food and Drugs Administration of China and ([dagger])Physiological Laboratory, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China Article History: Received 26 December 2005; revised 12 February 2006; accepted 13 February 2006. Article note: Correspondence: Dr Hong-Wei Yao, Zhejiang Respiratory Drugs Research Laboratory of State Food and Drugs Administration of China, School of Medicine, Zhejiang University, 353 Yan'an Road, Hangzhou 310031, People's Republic of China. Email: yhgwei@hotmail.com