右美托咪定对大鼠吗啡镇痛和耐受的影响

Effects of dexmedetomidine on morphine analgesia and tolerance in rats

目的探讨右美托咪定对大鼠吗啡镇痛和耐受的影响。方法雄性成年SD大鼠54只，采用随机数字表法，将其分为9组（n=6），对照组（C组）、吗啡组（M组）、右美托咪定组（D组）、MK-467组（右美托咪定抑制剂组）、右美托咪定加吗啡组（M＋D组）、MK-467加吗啡组（MK＋M组）、右美托咪定加吗啡耐受组（D＋MD组）、MK-467加吗啡耐受组（MK＋MD组）和吗啡耐受组（MD组）。皮下注射吗啡50mg／kg，1次／d，连续4d，建立吗啡耐受模型。于给药前1d测定热甩尾潜伏期（TFL）和热缩足反应潜伏期（TWL）。皮下注射吗啡5mg／kg后，腹腔分别注射右美托咪定和MK-467。每隔30min测定热甩尾潜伏期（TFL）和热缩足反应潜伏期（TWL）（0、30、60、90、120min）。结果与C组比较，M组、D组、M＋D组、D＋MD组和MD组TFL和TWL升高（P〈0．05）。与M组比较，M＋D组TFL和TWL升高（P〈0．05），与MD组比较，D＋MD组TFL和TWL升高（P〈0．05）。与M组比较，MK＋M组TFL和TWL降低（P〈O．05），与MD组比较，MK＋MD组TFL和TWL降低（P〈O．05）。结论右美托咪定可增强大鼠吗啡的抗伤害反应，并减轻吗啡耐受反应。

Objective To investigate the effects of dexmedetomidine on morphine analgesia and tolerance in rats. Methods Fifty-four healthy male Sprague-Dawley rats were randomly divided into 9 groups （n= 6 each）： control group （group C）, morphine group （group M）, dexmedetomidine group（group D）, MK-467 group （group MK）, dexmedetomidine 4- morphine group（group M4-D）, MK-467 ＋ morphine group（group MK4-M）, dexmedetomidine 4- morphine tolerance group（group D 4-MD）, MK-467 4- morphine tolerance group （group MK4-MD） and morphine tolerance group （group MD）. The rats were received morphine （50 mg/kg） once daily for 4 days in order to make the morphine tolerance model. Subcutaneous （sc） morphine （5 mg/kg）, then intraperitoneal dexmedeto- midine （20μg/kg） and MK-467 （0.25 mg/kg） were administered before the analgesia tests. Tail flick latency （TFL） and thermal paw withdrawal latency （TWL） were estimated at 1 d before drug administration and at 30 min intervals （0, 30, 60, 90,120 s）. Results Compared with those in group C , TFL and TWL were significantly increased in group M, group D, group M4-D, group D 4- MD and group MD（P〈0.05）. Compared with those in group M, TFL and TWL were significant- ly increased in group M4-D（P〈0.05）. Compared with those in group MD, TFL and TWL were sig- nificantly increased in group D4-MD（P〈0.05）. Compared with those in group M, TFL and TWL were significantly shortened in group MK＋M（P〈0.05）. Compared with those in group MD, TFL and TWL were significantly shortened in group MK＋MD（P〈0. 05）. Conclusion Dexmedetomidine can increase the antinociceptive effect of morphine and attenuate the tolerance to the analgesic effect of morphine.