不同剂量纳洛酮对吗啡致大鼠胃肠功能紊乱的影响

Effects of different doses of naloxone on morphine-induced gastro-intestinal dysfunction in rats

目的 探讨不同剂量纳洛酮对吗啡致大鼠胃肠功能紊乱的影响。方法 雄性SD大鼠84只，体重200～250g，随机分为7组（n=12），生理盐水对照组（NS组）单次皮下注射生理盐水4ml／kg；吗啡组（M组）单次皮下注射吗啡6mg／kg（混合于NS中，容积同NS组）；不同剂量纳洛酮（1幅／kg、100ng／kg、10ng／kg、1ng／kg和0．1ng／kg）混合吗啡（6mg／kg）组（MN1组、MN2组、MM组、MN4组和MN5组）：分别单次皮下注射混合药液4ml／kg（按照设定浓度将吗啡和纳洛酮混合于NS中）。各组随机取6只大鼠，于给药前、给药后30min、2、4、24h时测定血浆胃动素浓度。各组取6只大鼠，自由饮水、进食（饲料中混有高岭土），于进食后12、24h时测定高岭土摄入量和粪量。结果 与NS组比较，其余各组血浆胃动素浓度升高，高岭土摄入量增多，粪量减少（P〈0．01）；与M组比较．MN1组、MN2组和M心组血浆胃动素浓度降低，高岭土摄入量减少，粪量增多（P〈0．01）；与MN1组和MN2组比较，MN4组和MN5组血浆胃动素浓度升高，高岭土摄入量增多，粪量减少（P〈0．01）。结论 单次皮下注射纳洛酮1μg／kg、100ng／kg、10ng／kg可减轻吗啡致大鼠胃肠功能紊乱。

Objective To investigate the effects of different doses of naloxone on morphine-induced gastro-intestinal dysfunction. Methods Eighty-four male SD rats weighing 200-250 g were randomly divided into 7 groups （ n = 12 each） ： Ⅰ control group received subcutaneous normal saline （NS） 4 ml/kg; Ⅱ morphine group （M） received morphine 6 mg/kg S. C. ; group IH-Ⅳ received a mixture of naloxone （1 μg/kg, 100 ng/kg, 10 ng/kg, 1 ng/kg, 0.1 ng/kg） ＋ morphine 6 mg/kg（MN1-5 ）. Blood samples were taken from 6 animals in each group before and at 30 win, 2, 4 and 24 h after drug administration for determination of plasma motilin concentration. Six animals in each group were housed in a metabolism cage for 1 week with food and water available ad libitum for one week. The food contained kaolin. The kaolin intake and weight of feces were measured at 12 and 24 h after drug administration. Results The plasma motilin concentration was significantly lower in group MN1 , MN2 and MN3 than in group M. The kaolin intake was significantly lower and weight of feces significantly greater at 12 h after drug administration in group MN1 , MN2 and MN3 than in group M. Conclusion Naloxone 1 μg/kg, 100 ng/kg, 10 ng/kg can attenuate the gastro-intestinal dysfunction caused by morphine.