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大鼠酒精依赖或戒断后对丙泊酚半数有效剂量的影响
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| 篇名： | 大鼠酒精依赖或戒断后对丙泊酚半数有效剂量的影响 |
| TITLE： | |
| 摘要： | 目的：确定酒精依赖或戒断模型大鼠单次静脉注射丙泊酚的半数有效剂量（ED50），观察2倍ED50丙泊酚对其的麻醉效果。方法：取50只SD大鼠根据乙醇消耗量是否大于3.0 g/（kg·d）分为饮酒组（n＝23）和对照组（n＝27），饮酒组大鼠持续自由间断饮用乙醇建立酒精依赖模型，对照组大鼠只给予饮用水进行乙醇洗脱，2组大鼠各随机选取16只采用序贯法确定单次静脉注射丙泊酚的ED50，首剂量为6.02 mg/kg；洗脱1周后，选取撤离乙醇24 h出现酒精戒断表现的饮酒组大鼠纳入酒精戒断模型，同法确定酒精戒断组和对照组大鼠的丙泊酚ED50；洗脱1周后，观察酒精依赖组、酒精戒断组和对照组大鼠单次静脉注射2倍ED50剂量丙泊酚的麻醉效果[前爪翻正反射（FRR）消失时间、FRR复现时间和活动完全恢复时间]及其对应时间点和给药前的呼吸频率， 考察给药后48 h的肝功能指标（血清白蛋白、丙氨酸转氨酶、总胆红素、γ谷氨酰转肽酶）和肝组织形态学变化，每组10只。结果：酒精依赖模型大鼠丙泊酚的ED50为9.563 mg/kg，大于对照组的5.623 mg/kg；酒精戒断模型大鼠丙泊酚的ED50为4.086 mg/kg，小于对照组的5.297 mg/kg；与对照组比较，酒精依赖组和酒精戒断组大鼠的FRR复现时间均明显延长（P＜0.05），FRR消失时间和活动完全恢复时间差异无统计学意义（P＞0.05），FRR消失时的呼吸频率均小于注射丙泊酚前、FRR复现时和活动完全恢复时（P＜0.01）。注射2倍ED50剂量丙泊酚后，酒精依赖组和酒精戒断组FRR复现时间均长于对照组（P＜0.05），且酒精依赖组FRR复现时间长于酒精戒断组（P＜0.05）；酒精依赖组大鼠活动完全恢复时间长于对照组和酒精戒断组（P＜0.05）；3组大鼠FRR消失时的呼吸频率均小于注射丙泊酚前、FRR复现时和活动完全恢复时（P＜0.01），3组大鼠肝功能指标和肝组织形态学变化无明显差异。结论：大鼠酒精依赖后丙泊酚ED50增加，酒精戒断后ED50减小，2倍ED50剂量丙泊酚对其肝功能无明显毒性。 |
| ABSTRACT： | OBJECTIVE： To determine the median effective dose （ED50） of propofol with single intravenous injection in alcohol dependence or withdrawal model rats， and to observe the anaesthetic effect of 2-fold ED50 propofol. METHODS： Fifty SD rats were divided into drinking group （n＝23） and control group （n＝27） based on whether the consumption of alcohol was greater than 3.0 g/（kg·d）. Drinking group continued to drink freely and intermittently to establish alcohol dependence model. Control group was only given drinking water for ethanol elution. 16 rats were randomly selected from each group to determine ED50 of propofol with single intravenous injection by sequential method， and initial dose was 6.02 mg/kg. After eluting for a week， alcohol dependence rats stopped drinking for 24 hours and had alcohol withdrawal symptoms to establish alcohol withdrawal model. ED50 of propofol in alcohol withdrawal group and control group were determined with same method. After eluting for a week， anaesthetic effect [disappearance time and reappearance time of forepaw righting reflex （FRR）， time of activity complete recovery] of 2-fold ED50 propofol with single intravenous injection were observed in alcohol dependence group， alcohol withdrawal group and control group， and corresponding time point and the frequency of respiration before administration were also observed. Changes of liver function indexes （serum albumin， alanine transaminase， total bilirubin， γ glutamyl transaminopeptidase） and liver histomorphology were observed 48 h after medication， 10 in each group. RESULTS： ED50 of propofol in alcohol dependence model rats was 9.563 mg/kg， which was higher than 5.623 mg/kg of control group. ED50 of propofol in alcohol withdrawal model rats was 4.086 mg/kg， which was lower than 5.297 mg/kg of control group. Compared with control group， reappearance time of FRR was prolonged significantly in alcohol dependence group and alcohol withdrawal group （P＜0.05）. There was no statistical significance in disappearance time of FRR or activity complete recovery time （P＞0.05）. The frequency of respiration during FRR disappearance was lower than before propofol injection， FRR reappearance and activity complete recovery （P＜0.01）. After intravenous injection of 2-fold ED50 propofol， reappearance time of FRR in alcohol dependence group and alcohol withdrawal group were longer than control group （P＜0.05）； the alcohol dependence group was longer than the alcohol withdrawal group （P＜0.05）. The time of activity complete recovery in alcohol dependence group was longer than control group and alcohol withdrawal group （P＜0.05）. The frequency of respiration in 3 groups during FRR disappearance were all lower than before propofol injection， FRR reappearance and activity complete recovery （P＜0.01）. There was no significant difference in the change of liver function indexes or liver histomorphology. CONCLUSIONS： ED50 of propofol is increased in alcohol dependence rats， while ED50 of propofol is decreased in alcohol withdrawal rats. 2-fold ED50 of propofol has no significant toxicity to liver function. |
| 期刊： | 2018年第29卷第9期 |
| 作者： | 张莉，谭华，罗晨禹，刘英海，巩固，吴畏 |
| AUTHORS： | ZHANG Li，TAN Hua，LUO Chenyu，LIU Yinghai，GONG Gu，WU Wei |
| 关键字： | 序贯法；丙泊酚；酒精依赖；酒精戒断；半数有效剂量；大鼠 |
| KEYWORDS： | Sequential method； Propofol； Alcohol dependence； Alcohol withdrawal； Median effective dose； Rat |
| 阅读数： | 502 次 |
| 本月下载数： | 3 次 |
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