不同剂量舒芬太尼在大鼠中的麻醉效果和药动学研究

Anesthetic effects and pharmacokinetics of different doses of sufentanil in rats

目的研究不同剂量舒芬太尼在大鼠中的麻醉效果和药动学特征。方法将30只雄性SD大鼠随机分为6组,每组5只,B^F组分别尾静脉注射舒芬太尼20、 40、 80、 160、 320μg·kg^-1, A组以等体积的生理盐水作为对照。测定翻正反射消失和恢复、夹趾反射消失和恢复的时间以评价麻醉效果,测定翻正反射恢复后共济失调时间以观察麻醉恢复程度,同时监测麻醉期间大鼠的心率、呼吸频率、体温并检测麻醉结束后大鼠肝肾功能指标的变化。采用液相色谱-质谱联用(LC/MS)法定量检测给药后大鼠血浆中舒芬太尼的浓度,拟合药动学曲线。结果随着舒芬太尼的剂量增加,大鼠翻正反射和夹趾反射的消失时间缩短,恢复时间增长,共济失调期相应延长。D^F组B麻醉起效时间和达到深度麻醉的时间均显著短于B组(P<0.05),而深度麻醉、麻醉维持时间及麻醉恢复时间均显著长于B组(P<0.05)。注射后E、F组大鼠的心率、呼吸频率和体温显著降低,丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平显著高于A组(P<0.05), D组大鼠生命活动正常,与A组相比ALT和AST无显著增高(P>0.05)。不同剂量舒芬太尼在大鼠体内的半衰期相近,约为2.2h。结论舒芬太尼80μg·kg^-1具有较好的麻醉效果和体内安全性,是大鼠麻醉的合适浓度,且给药剂量不影响舒芬太尼在大鼠体内的半衰期。

AIM To study the anesthetic effects and pharmacokinetic characteristics of different doses of sufentanil in rats. METHODS Thirty male SD rats were randomly divided into 6 groups, 5 rats in each group.The rats were respectively injected with sufentanil at a dose of 20, 40, 80, 160, 320 μg·kg^-1 via the tail vein in group B-F, and equal volume of normal saline was used as the control in group A. The time of the disappearance and recovery of the righting reflex and the clip toe reflection were measured to evaluate the anesthesia effect. The ataxia time after the recovery of the righting reflex was measured to observe the recovery degree of anesthesia. Meanwhile, the heart rate, respiratory rate and body temperature of the rats during anesthesia were monitored and the changes of liver and kidney function indexes after anesthesia were detected.Liquid chromatography-mass spectrometry( LC/MS) was used to determine the concentration of sufentanil in plasma. RESULTS With the increase of sufentanil dose, the disappearance time of the righting reflex and the clip toe reflex was shortened, the recovery time was increased, and the ataxia period was prolonged. The time of onset of anesthesia and the time to reach deep anesthesia were significantly shorter in the group D-F than in the group B(P < 0.05), and the deep anesthesia, anesthesia maintenance and anesthesia recovery time were significantly longer than the group B(P < 0.05). The heart rate, respiratory rate and body temperature of the group E and F were significantly lower, and the levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were significantly higher than the group A(P < 0.05). However, the life activities of the rats in the group D were normal, and there was no significant increase in ALT and AST level compared with the group A(P > 0.05). The metabolic half-life of sufentanil in different doses were similar in rats, about 2.2 h.CONCLUSION Sufentanil 80 μg·kg^-1 has good anesthetic effect and safety in vivo, which can be a suitable concentration for anesthesia in rats, and the dose does not affect the half-life.