CAJ | 학술논문

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200～250 g,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10 mg/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30 min给予生理盐水10 ml/kg灌胃,连续5 d;RC组、R1组、R2组和R3组每天皮下注射生理盐水或吗啡前30 min分别给予10.0、0.4、2.0和10.0 mg/kg瑞舒伐他汀灌胃,连续5d.模型制备前1 d(T1)和制备后1 d(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L5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R3组差异无统计学意义(P＞0.05)；与MT组相比,RC组、R2组和R3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.
목적 탐토서서벌타정대대서마배내적영향.방법 웅성SD대서48지,체중200～250 g,채용수궤수자표법,장대서수궤분위6조(n=8):대조조(C조)、마배내수조(MT조)、서서벌타정대조조(RC조)화불동제량서서벌타정처리조(R1조～R3조).매천8:00화16:00피하주사마배10 mg/kg,련속5d,제비마배내수모형.C조화RC조급여등량생리염수.C조화MT조매천피하주사생리염수혹마배전30 min급여생리염수10 ml/kg관위,련속5 d;RC조、R1조、R2조화R3조매천피하주사생리염수혹마배전30 min분별급여10.0、0.4、2.0화10.0 mg/kg서서벌타정관위,련속5d.모형제비전1 d(T1)화제비후1 d(T2)측정열축족잠복기,계산최대진통효응백분비(MPE)；T2시통역측정결속후,처사대서,취L5척수,채용Western blot법측정척수세포외조절단백격매(ERK)、린산화세포외조절단백격매(p-ERK)적표체수평,채용ELISA법측정이급백세포개소1β(IL-1β)화종류배사인자α(TNF-α)적함량.결과 여C조상비,MT조화R1조T2시MPE강저,척수p-ERK、IL-1β화TNF-α수평승고(P＜0.05),RC조、R2조화R3조차이무통계학의의(P＞0.05)；여MT조상비,RC조、R2조화R3조T2시MPE승고,척수p-ERK、IL-1β화TNF-α수평강저(P＜0.05),R1조차이무통계학의의(P＞0.05).R2조화R3조상술지표비교차이무통계학의의(P＞0.05),6조대서척수ERK표체수평차이무통계학의의(P＞0.05).결론 서서벌타정가감경대서마배내수,기궤제가능여억제척수ERK린산화급강저IL-1β화TNF-α수평유관.
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 divided 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 R1),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 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups RC,R1,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 expression of extracellular signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK)(by Western blot) and contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (by ELISA).Results 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 significantly increased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were decreased in groups RC,R2 and R3 (P ＜ 0.05).There was no significant difference in the indicators mentioned above between groups R2 and R3,and in the expression of ERK between the six groups (P ＞ 0.05).Conclusion Rosuvastatin can attenuate the morphine tolerance in rats by inhibiting the phosphorylation of ERK and decreasing the level of IL-1β and TNF-α.