Effect of lovastatin on shedding of heparan sulfate proteoglycan and syndecan-1 in lung tissues of rats with sepsis-induced acute lung injury

Abstract

Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1(SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury. Methods One-hundred and twenty male Wistar rats aged 8-12 weeks, weighing 325-425 g, were randomly divided into 3 groups (n =40 each) using a random number table: sham operation group (group S), cecal ligation and puncture (CLP) group and lovastatin group (group L). Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups, while the equal volume of 0.5% CMC (the solvent) was given in CLP group. Sepsis was produced by CLP on 5th day of administration in CLP and L groups. The left lung was lavaged at 24 h after operation. The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations, white blood cell (WBC) count and percentage of neutrophils. Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA). Evans blue was injected at 24 h after operation in the remaining 20 rats of each group. The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR), and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue. Results Compared with group S, the protein concentrations, WBC count and percentage of neutrophils in BALF, Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased, and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups. Compared with group CLP, the protein concentrations, WBC count and percentage of neutrophils in BALF, Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased, and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L. The pathological changes of lungs were significantly attenuated in group L as compared with group CLP. Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats. Key words: Lovastatin; Sepsis; Respiratory distress syndrome, adult; Heparan sulfateproteoglycans; Syndecan-1