Effects of Alcohol Dependence or Withdrawal on Median Effective Dose of Propofol in Rats / 中国药房

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.