Mechanism of simvastatin-induced improvement of permeability of pulmonary microcirculation in septic rats: the relationship with VEGF-α / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between the mechanism of simvastatin-induced improvement of permeability of pulmonary microcirculation and vascular endothelial growth factor α (VEGF-oα) in septic rats.Methods Eighty clean-grade healthy female Wistar rats,aged 49-63 days,weighing 200-250 g,were divided into 4 groups using a random number table method:control group (group C,n =8),sham operation group (group Sham,n =24),sepsis group (group Sep,n =24) and simvastatin group (group S,n =24).Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized rats.Simvastatin 20 mg/kg was injected to the stomach once a day for two weeks before CLP in group S,and the equal volume of normal saline was given instead in the other groups.Rats were sacrificed after anesthesia in group C,and 8 rats selected at 6,24 and 48 h after CLP were sacrificed after anesthesia in the other three groups,and blood samples and lung specimens were collected.The concentrations of VEGF-α and intercellular adhesion molecule-1 (ICAM-1) in serum were measured by enzyme-linked immunosorbent assay.The wet/dry lung weight ratio (W/D ratio) was determined,and the expression of VEGF-α in lung tissues was detected by immunohistochemistry.Results Compared with group C,W/D ratio was significantly increased,the expression of VEGF-α was up-regulated,and the concentrations of serum ICAM-1 were increased in Sep and S groups,the concentration of serum VEGF-α was increased in group Sep (P＜0.05),no significant change was found in serum VEGF-α concentrations in group S,and no significant change was found in the parameters mentioned above in group Sham (P＞0.05).Compared with group Sep,W/D ratio was significantly decreased,the expression of VEGF-α was down-regulated,and the concentrations of serum VEGF-α and ICAM-1 were decreased in group S (P＜0.05).Conclusion The mechanism by which simvastatin improves permeability of pulmonary microcirculationis associated with the decreased level of VEGF-α in local lung tissues and peripheral blood of septic rats.