氟比洛芬酯静脉注射后在大鼠手术切口部位肌肉组织中的分布

Distribution of flurbiprofen axetil in the muscle tissue in surgical field after intravenous administration in rats

目的评价氟比洛芬酯静脉注射后在大鼠手术切口部位肌肉组织中的分布。方法清洁级雄性SD大鼠40只，体重240～260g，随机分为5组（n=8）：切口痛组（IP组）和不同剂量氟比洛芬酯组（F1-4组）。建立大鼠切口痛模型后20min时IP组经尾静脉注射生理盐水0．5ml，F1-4组经尾静脉分别注射氟比洛芬酯2、4、8和16mg／kg。于尾静脉注射结束后2h时，采用反相高效液相色谱法测定肌肉氟比洛芬含量，采用ELISA法测定前列腺素E2（PGE2）含量。结果与非手术侧比较，F1-4组手术侧足底肌肉组织氟比洛芬和PGE含量、IP组手术侧PGE2含量升高（P〈0．01）；与IP组比较，F1-4组手术侧足底肌肉组织PGE2含量降低（P〈0．05），F4组非手术侧足底肌肉组织PGE2含量降低，F1-3组非手术侧上述指标差异无统计学意义（P〉0．05）；F1组、F2组、F3组和F4组手术侧足底肌肉组织氟比洛芬和PGE2含量依次升高，F4组非手术侧足底肌肉组织氟比洛芬和PGE2含量高于F1组、F2组和F3组（P〈0．05或0．01），F1组、F2组和F3组非手术侧上述指标比较差异无统计学意义（P〉0．05）。结论氟比洛芬酯静脉注射后在大鼠手术切口部位肌肉组织中的分布高于非手术侧，提示氟比洛芬酯具有靶向镇痛作用。

Objective To determine the distribution of flurbiprofen axetil in the muscle tissue in the surgical field after intravenous administration in rats. Methods Forty pathogen-free male SD rats weighing 240- 260 g were randomly divided into 5 groups （ n = 8 each） ： [ control group （group C） and Ⅱ -Ⅴ flurbiprofen groups received iv flurbiprofen axetil 2, 4, 8, 16 mg/kg respectively （group F1 , F2, F3, F4 ） . An 1 cm long incision was made in the right plantar surface from the heel to the toes according to the method described by Brennen under isoflurane anesthesia. The muscle was cut through in the incision but not severed. Flurbiprofen axetil was injected iv via the vein in the tail at 20 min after plantar incision was made in group Ⅱ - Ⅴ . At 2 h after iv flurbiprofen axetil administration, the animals were anesthetized with intraperitoneal 3% pentobarbital 100 mg/kg. The muscles of both hindpaws were dissected, homogenized and centrifuged. The supernatant was separated for determination of flurbiprofen content （by RP-HPLC） and PGE2 content （by ELISA）. Results The flurbiprofen content in the muscle of hindpaw on the operated side was significantly increased dose-dependently compared with that on the non-operated side and was significantly higher than that on the non-operated side. The flurbiprofen content in the muscle of hindpaw on the non-operated side was significantly higher in group F4 than in the other 4 groups. There was no significant difference in the flurbiprofen content in the paw muscle on the nonoperated side among group C, F1 F2 and F3 . The PGE2 content was significantly higher in the hindpaw muscle on the operated side than that on the non-operated side, and was significantly decreased by flurbiprofen dosedependently. Conclusion The content of flurbiprofen is significantly higher in the muscle tissue in the surgical field after iv administration than that on the non-operated side, indicating that flurbiprofen axtei has target-analgesic effect.