中文摘要：

目的探讨瑞舒伐他汀对大鼠吗啡耐的影响。方法雄性SD大鼠48只，体重200～250g，采用随机数字表法，将大鼠随机分为6组（n=8）：对照组（C组）、吗啡耐受组（MT组）、瑞舒伐他汀对照组（RC组）和不同剂量瑞舒伐他汀处理组（R1组～R3组）。每天8：00和16：00皮下注射吗啡10mg／kg，连续5d，制备吗啡耐受模型。C组和RC组给予等量生理盐水。C组和MT组每天皮下注射生理盐水或吗啡前30min给予生理盐水10ml／kg灌胃，连续5d；RC组、R1组、R2组和R3组每天皮下注射生理盐水或吗啡前30min分别给予10．0、0．d、2．0和10．0mg／kg瑞舒伐他汀灌胃，连续5d。模型制备前1d（T1）和制备后1d（T2）测定热缩足潜伏期，计算最大镇痛效应百分比（MPE）；T2时痛阈测定结束后，处死大鼠，取k脊髓，采用Western blot法测定脊髓细胞外调节蛋白激酶（ERK）、磷酸化细胞外调节蛋白激酶（p-ERK）的表达水平，采用ELISA法测定以及白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF—α）的含量。结果与C组相比，MT组和R1组T2时MPE降低，脊髓p-ERK、IL-1β和TNF-α水平升高（P〈0．05），RC组、R2组和R2组差异无统计学意义（P〉0．05）；与MT组相比，RC组、避组和R2组T2时MPE升高，脊髓p-ERK、IL-1β和TNF-α水平降低（P〈0．05），R1组差异无统计学意义（P〉0．05）。R2组和R3组上述指标比较差异无统计学意义（P〉0．05），6组大鼠脊髓ERK表达水平差异无统计学意义（P〉0．05）。结论瑞舒伐他汀可减轻大鼠吗啡耐受，其机制可能与抑制脊髓ERK磷酸化及降低IL-1β和TNF-α水平有关。

英文摘要：

Objective To investigate the effect of rosuvastatin on the morphine tolerance in rats and the underlying mechanism. Methods Forty-eight male Sprague-Dawley rats, weighing 200-250 g, were randomly di- vided into 6 groups （n = 8 each）： control group （group C）, morphine tolerance group （group MT）, rosuvastatin control group （group RC）, rosuvastatin 0.4 mg/kg group （group R 1 ）, rosuvastatin 2.0 mg/kg group （group R2 ） and rosuvastatin 10.0 mg/kg group （group R3 ） Morphine tolerance was induced by subcutaneous injection of morphine 10.0 mg/kg at 8 ： 00 and 16 ： 00 everyday for 5 consecutive days. The equal volume of normal saline was given in groups C and RC. Normal saline 10 ml/kg was injected through a gastric tube into stomach everyday at 30 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups C and MT. Rosuvastatin 10, 0.4, 2.0 and 10.0 mg/kg were injected through a gastric tube into stomach everyday at 30 rain after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups RC, Rl , R2 and R3 , respectively. The paw withdrawal latency to nociceptive thermal stimulation was measured 1 day before （T1） and 1 day after morphine tolerance was induced （T2）. The percentage of maximal possible effect （MPE） was calculated. The rats were sacrificed after the last measurement of pain threshold and the L5 segment of the spinal cord was removed for determination of the exprsion of extracellular signal-regulated kinase （ERK） and phosphorylated ERK （p-ERK） （by Western blot） and contents of interleukin-1β （IL-1β） and minor necrosis factor-α （TNF-α） （by ELISA）.Resuits Compared with group C, MPE was significantly decreased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were increased in groups MT and R1 （ P 〈 0.05）. Compared with group MT, MPE was siguifi eanfly increased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were decreased in groups