模拟航海刺激对大鼠丙泊酚麻醉敏感性的影响及机制探讨

Effect and mechanism of simulated ship motion on the anesthetic sensitivity of propofol in rats

目的探讨模拟航海刺激对大鼠丙泊酚麻醉敏感性的影响，为海上环境下丙泊酚的合理使用提供依据。方法以大鼠条件性厌食症作为判断指标，采用仿制Crampton旋转刺激器制作大鼠运动病模型。研究包含两部分：（1）150只SD大鼠按数字表法随机平分为对照组和旋转组，再根据丙泊酚使用剂量不同将2组大鼠分为150、200、250、300、400mg／kg5个亚组（每组n=15），观测大鼠活动和行为变化、大鼠入睡率、睡眠潜伏期、睡眠持续时间等。（2）32只SD大鼠按数字表法随机分为对照组（I组）、旋转组（Ⅱ组）、麻醉组（Ⅲ组）和旋转后再麻醉组（IV组），每组8只，分别检测4组大鼠之大脑皮层、下丘脑和海马组织的乙酰胆碱、去甲肾上腺素、γ-氨基丁酸及谷氨酸含量。结果在150～250mg／kg范围内，随着使用剂量的增加，丙泊酚对大鼠的镇静作用逐步加强（P〈0．01）。当丙泊酚剂量为150、200、250mg／kg时，旋转组和对照组大鼠睡眠持续时间分别为（21．33±8．08）、（67．67±21．07）、（97．38±23．79）min和（13．15±7．64）、（42．60±20．79）、（73．404-21．28）min，组间比较其差异均有统计学意义（P〈0．01）。中枢神经递质的变化趋势是：在大脑皮层和下丘脑组织，Ⅱ组主要体现为升高，Ⅲ组主要表现为降低，Ⅳ组则有“强化”Ⅲ组的作用，使各神经递质数值更进一步降低；在海马组织，与I组相比，其他各组神经递质均有降低，其均值为I组〉II组〉III组〉IV组。结论在临床常用剂量（150—250mg／kg）范围内，模拟航海刺激可明显增加大鼠对丙泊酚麻醉的敏感性，但其作用机制尚需进一步研究。

Objective To explore the effect of simulated ship motion on the anesthetic sensitivity of propofol in rats, so as to provide evidence for rational application of propofol during deployment at sea. Methods The motion sickness model was developed by using the rotating-chair test. The study consisted of 2 parts. （ 1 ） One hundred and fifty SD rats were randomly divided into the control and the rotation groups, which were further divided into 5 sub-groups, each consisting of 15 animals, in accordance with the dosage of propofol used. The activity and behavior, rate of sleep, sleep latency and sleep duration of rats were closely observed. （2） Thirty-two SD rats were randomly divided into the control group （ group 1 ）, the rotation group （ group 2）, the anesthesia group （ group 3 ） and the rotation plus anesthesia group （ group 4）, each consisting of 8 animals. The acetylcholine （Ach）, norepinephrine （NE）, γ-aminobutyric acid （GABA）, glutamic acid （Glu） in the brain cortex, thalamus and hippocampus were determined respectively in the four animal groups. Results Within the dosage levels of 150 mg/kg -250 mg/kg, the sedative effect of propofol increased progressively with the increase of dosage （P 〈 0. 01 ）. When propofol levels reached 150 mg/kg,200 mg/kg and 250 mg/kg, the sleep time for the rotation group was （21.33 ± 8.08 ）, （67.67 ± 21.07 ） and （97.38 ± 23.79）/min, and the sleep time for the control group was （ 13. 15 ±7. 64）, （42. 60 ± 20. 79） and （ 73.40 ± 21.28 ）/ rain respectively （P 〈 0.01 ）. And there was statistical significance, when comparisons were made between the groups （P 〈 0.01 ）. The following predominant tendency could be seen in the change of neurotransmitters： in the brain cortex and thalamus, the neurotransmitter level was elevated for the animals in group 2, the neurotransmitter level was decreased for the animals of group 3 and it was further decreased for the animals of group 4; In hippocampus, the neurotransmitter levels in all other groups were also decreased, when comparisons were made with that of group 1, with an average value of group 1 〉 group 2 〉 group 3 〉 group 4. Conclusions In clinical application of general dosage of 150 mg/kg -250 mg/kg, simulated ship motion could obviously increase the anesthetic sensitivity of propofol in rats, however the mechanism involved should be further studied.