RESUMO
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.