目的 探讨辛伐他汀预处理对脓毒症大鼠胸主动脉诱导型一氧化氮合酶(iNOS)及内皮型一氧化氮合酶( eNOS)表达的影响.方法 清洁级雌性Wistar大鼠80只,4月龄,体重200～250 g,采用随机数字表法,将其随机分为4组:正常对照组(Ⅰ组,n=8)、假手术组(Ⅱ组,n=8)、脓毒症组(Ⅲ组,n=32)和辛伐他汀预处理组(Ⅳ组,n=32).Ⅱ组打开腹腔找到盲肠后还纳腹腔,缝合腹壁切口.Ⅲ组和Ⅳ组采用盲肠结扎穿孔法制备大鼠脓毒症模型.Ⅳ组制备脓毒症模型前经胃管灌注辛伐他汀20 mg/kg,1次/d,连续2周,Ⅰ组～Ⅲ组给予等容量生理盐水.Ⅱ组于假手术后6h处死动物,Ⅲ组和Ⅳ组于盲肠结扎穿孔后3、6、24、48 h分别取8只动物,处死,取胸主动脉,采用Western blot法测定iNOS和eNOS表达水平.结果 与Ⅰ组比较,Ⅱ组iNOS和eNOS表达差异无统计学意义(P＞0.05),Ⅲ组和Ⅳ组iNOS表达上调,eNOS表达下调(P＜0.05)；与Ⅲ组比较,Ⅳ组iNOS表达下调,eNOS表达上调(P＜0.05).结论 辛伐他汀预处理可下调脓毒症大鼠血管内皮细胞iNOS表达和上调血管内皮细胞eNOS表达,对血管内皮细胞功能有保护作用.%Objective To investigate the effects of simvastatin preconditioning on the expression of inducible and endothelial nitric oxide synthase ( iNOS,eNOS) in thoracic aorta in a rat model of sepsis.Methods Eighty pathogen-free female Wistar rats aged 4 months weighing 200-250 g were randomly divided into 4 groups:group normal control (group Ⅰ,n =8) ; group sham operation (group Ⅱ,n =8) ; group sepsis (group Ⅲ,n =32) and group simvastatin preconditioning (group Ⅳ,n =32).Sepsis was induced by cecal ligation and puncture (CLP) in groups Ⅲ and Ⅳ.In group Ⅳ simvastatin 20 mg/kg was given via a gastric tube once a day for 2 weeksbefore CLP.The thoracic aorta specimens were taken at 3,6,24 and 48 h after CLP (n =8 at each time point)for detection of iNOS and eNOS protein expression by Western blot analysis.Results CLP significantly up-regulated iNOS expression and down-regulated eNOS expression in group Ⅲ as compared with groups Ⅰ and Ⅱ.Simvastatin pretreatment significantly attenuated CLP-induced increase in iNOS expression and decrease in eNOS expression in group Ⅳ as compared with group Ⅲ.Conclusion Simvastatin preconditioning can protect vascular endothelial cells from septic injury by down-regulating iNOS expression and up-regulating eNOS expression in vascular endothelial cells.
展开▼
