Pharmacokinetic Study Of Ethanol In Rats And The Mechanisms Of Ethological Effect On Rats

Background & ObjectiveIn recent years,with the improvement of our living standard,the consumption of alcohol tends to be more than ever,which has caused the incremental variety of civil cases,criminal cases and traffic accidents.Chronic alcoholism has been reported by many researchers at home and abroad,but the mechanisms of ethological effects caused by acute alcoholism and its behavioral alteration in the experimental circumstance had rarely been reported.Large-scale systems of our body such as blood system,digestive system,central nervous system,and so on,would be impacted of various degrees after acute alcohol consumption.The metabolism of ethanol in the body is also influenced by the differences in race,gender,the mount of alcohol consumption and other factors.As we know,a certain concentration of ethanol will affect people's ability to control their own behavior,But how much ethanol would result in hazardous drive behavior still keeps obscure on research at present;as ethanol tolerance varies in different individuals,it is difficult to be evaluated by a consistent standard;Penalties to the drunk driving and drunken driving have been enacted in our traffic laws and regulations,as a result of effect of ethanol metabolism, it could arrive at driving under influence of alcohol standart when traffic accident happening,but it short of standard to detect dose of ethanol,as a result made drivers escape from punishment.Therefore,further study of the behavior of ethanol and its mechanism,to clarify the relationships between the ethological alternation and pharmacokinetic of the ethanol in vivo,have much practical meaning and clinical significance.Methods1.According to the ratio of 4ml/kg,8ml/kg,16ml/kg perfused to rats respectively to produce low,medium and high doses of acute alcoholism model,the corresponding control group was given the correspond volume of normal saline.2.To detect ethological changes of rats with different concentrations of ethanol and timing through the power Y maze.3.Using immunohistochemistry to detect c-fos and c-jun expression in the cerebral nerves cell of rats with different concentrations of ethanol. 4.To detect concentration of ethanol in rats apply gas chromatography,according to metabolism of ethanol in rats to estimate compartment model and the pharmacokinetic parameters.5.Statistical analysis:the data were dealt with SPSS10.0 statistical software package,and the measurement data were indicated with mean±standard deviation((?)+s).Comparing groups used one-way ANOVA,LDS～t test when with normal distribution and homogeneity,and non-parametric test when with non-normal distribution and irregular variance.The analysis of correlation was performed with Pearson test and a value of P＜0.05 was considered as statistical significant.Results1.Ethological change in rats:at Oh after perfused,the fault frequency that rats of each group escaped the electric shock reflection were normal,the comparison among groups was not statistically significant(P＞0.05);0.5h,1h,2h,4h,8h,12h after perfused,the fault frequency that rats escaped the electric shocks reflection emerged changes of different levels,the comparison among groups was statistically significant (P＜0.05);After perfused 24 hours,the fault frequency that rats of each group escaped the electric shocks reflection returned to normal,the comparison among groups was not statistical significance(P＞0.05).Along with the variance of time,the fault frequency that rats of each group escaped the electric shock reflection presented a prominent regularity,the fault frequency that rats perfused after 2h escaped the electric shock reflection was the most in 4ml/kg group,the fault frequency that rats perfused after 4h escaped the electric shock reflection was the most in 8ml/kg Group and 16ml/kg group.As time passing by,4ml/kg,8ml/kg,16ml/kg group after perfused 8h,12h,24h respectively returned to normal.2.The changes of HE staining of rat brain tissue:the corresponding control group and low-dose group at different time have not been obviously pathological changes in brain tissue;Middle-dose group changed more obvious after 4h and 8h, showing distend vasodilatation and hyperemia in the brain tissue,the lacunae widen of nerve cells and small blood vessels;High-dose group changed the most obviously, besides the above changes the cytoplasm stained lightly,and there were scattered red blood cells in apart regional after 2h,4h,8h.3.The expressions of c-fos and c-jun in rat cerebral nerves cell: immunohistochemistry control group showed that the nucleus presented light blue; Positive reaction locates mainly in the nucleus.Counting positive cells reflected positive reaction;the intensity of expressions was different.Along with the variance of time,the expression of c-fos and c-jun presented a prominent regularity,rats perfused after 2h,each of group appeared c-fos,c-jun expression,c-fos and c-jun expressed strong in high-dose group after 4h,nucleus stained deeply,which had been statistically significant(P＜0.05) to compared with experimental control group and low-dose group.The expression was decrease at 8h,low concentration group returned to the level of experimental control group,and the expression of c-fos and c-jun in middle low-dose group also returned to the level of the control group after 24h.4.The analytic method of Pharmacokinetic of alcohol in rats:The foreign matter of blood plasma didn't interfere with the detection of ethanol,and the specificity, reproducibility,accurate,stability,good separation of the detection method made it consistented with requirement of biological specimen detected.The method could be used for the analyses of alcohol in rats' blood plasma.5.The pharmacokinetic parameters' difference of alcohol in different dosage groups:The parameters that relate to absorption and distribution such as Cmax,V,AUC0-T,AUC0-∞were statistically significant(P＜0.05) in different dosage groups. A simple correlation test was implemented to analyze the relationship of dosage and AUC,C_max,the result of which showed that they had a positive correlation relationship,the coefficient correlation were 0.512(P＜0.01),0.688(P＜0.01).Each parameter increased when dosage increasing.The rate constant relating to elimination of medicine.Ke,T_1/2ke were statistically significant(P＜0.05) among different dosage groups,and CL didn't show statistical significance(P＞0.05).Conclusions1.Acute ethylism could cause learning and memory dysfunction in rats,and the degree is related with the concentration of ethanol,the fault frequency is related with the role of the time closely;After the same concentration of ethanol perfused in rats, the fault frequency that rats escape the electric shock reflection also varied at different times.2.Ethanol could induce the expression of c-fos and c-jun in the cerebral nerves cell,and the intension of expression is related with the concentration of ethanol,at the same time is closely related with the time.3.The pharmacokinetics parameters of alcohol in each dosage groups fitted with one-compartment model;there is correlation relationship between metabolism and dosage.4.The peak of ethology error hysteresis with the time of ethanol peak concentration of blood emerged...