活性炭对百草枯经口中毒的吸附效果评价:一项大型动物的实验研究
Evaluation of adsorption effect of activated charcoal on oral paraquat poisoning: an experimental study on large animal
摘要目的 探讨活性炭混悬液对百草枯(PQ)染毒比格犬胃肠道内PQ的吸附效果.方法 将12只健康雄性比格犬按随机数字表法分为对照组和实验组,每组6只.两组比格犬均采用20% PQ溶液30 mg/kg灌胃.实验组于PQ染毒后30 min给予活性炭混悬液灌胃(Ⅰ型活性炭粉1.0 g/kg用生理盐水100 mL混匀),对照组灌胃等量生理盐水.两组于PQ染毒后10 min、30 min及1、2、4、8、12、24、48 h采集肝门静脉血和外周静脉血,观察血浆PQ水平变化,采用DAS 2.1.1药代动力学分析软件分析两组毒代动力学参数的变化.于染毒前10 min及染毒后4h和1~7d动态监测心率(HR)、呼吸频率(RR)、脉搏血氧饱和度(Sp02)等生命体征的变化.结果 PQ灌胃染毒后,对照组肝门静脉血和外周静脉血血浆PQ水平迅速升高,4h达高峰后迅速降低,8h后缓慢下降;但实验组达峰速率明显减慢,且PQ峰值较对照组明显降低,约为对照组的50%(μg/L:肝门静脉血为123.50±11.67比255.18±12.29,外周静脉血为122.35±11.72比250.86±11.15),8h后下降速度明显快于对照组,48 h血浆PQ水平明显低于对照组(μg/L:肝门静脉血为0.53±0.18比15.98±5.58,外周静脉血为0.31±0.01比15.03±4.82,均P<0.01).毒代动力学分析显示,与对照组比较,实验组肝门静脉血和外周静脉血血浆PQ峰浓度(Cmax)和药时曲线下面积(AUC)均显著降低[Cmax (μg/L):肝门静脉血为125.07±9.49比255.18±12.29,外周静脉血为123.38±9.52比250.86±11.15;AUC (mg· L-1· h-1):肝门静脉血为1.6±0.2比3.3±0.4,外周静脉血为1.5±0.2比3.2±0.3],PQ达峰时间(Tmax)较慢(h:肝门静脉血为5.3±1.9比4.0±0.0,外周静脉血为4.7±1.5比4.0±0.0),PQ表观血浆半衰期(t1/2)和平均驻留时间(MRT)较短[t1/2(h):肝门静脉血为3.8±1.2比15.4±3.7,外周静脉血为3.5±1.0比15.5±2.7;MRT(h):肝门静脉血为8.0±1.5比13.4±1.2,外周静脉血为7.6±1.3比13.3±1.2,均P<0.01].PQ染毒后两组比格犬HR和RR均呈逐渐加快趋势,4d左右达峰值后逐渐减慢;SpO2呈逐渐降低趋势,4d左右达谷值后逐渐恢复;但实验组生命体征变化幅度较小,各项指标均优于对照组[4dHR(次/min):134.50±3.04比142.00±6.43,4dRR(次/min):31.00±0.58比34.33±0.94,4 d SpO2:0.900±0.006比0.873±0.005,均P<0.05].结论 PQ染毒后30 min给予活性炭可减缓比格犬血浆PQ水平升高速率,降低峰浓度,对生命体征影响较小.
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abstractsObjective To study the adsorption effect of activated charcoal suspension on paraquat (PQ) in gastrointestinal tract of beagles exposed to PQ.Methods Twenty healthy male beagles were randomly divided into experimental group and control group,with 6 beagles in each group.20% PQ solution (a dose of 30 mg/kg) was prescribed through stomach for beagles in both groups.After exposure to PQ for 30 minutes,the beagles in experimental group were given activated charcoal suspension (1.0 g/kg of type Ⅰ activated charcoal powder mixed with 100 mL of normal saline) by gavage,while the control group was only given equal volume of normal saline.After exposure to PQ for 10 minutes,30 minutes,and 1,2,4,8,12,24,and 48 hours,blood was collected from hepatic portal veins and peripheral veins to detect the PQ concentration change in the plasma.The toxicokinetics software DAS 2.1.1 was applied to analyze PQ concentration and compare the change in toxicokinetics parameters between the both groups.The change in vital signs including heart rate (HR),respiratory rate (RR) and pulse oxygen saturation (SpO2) was dynamically monitored 10 minutes before exposure,4 hours and each day from the 1st to the 7th day after exposure.Results After exposure to PQ,the poison concentration in the plasma of hepatic portal veins and peripheral veins in the control group rose quickly and reached peak 4 hours later.It fell quickly at first,and fell slowly 8 hours later.But in the experimental group,the increase rate to the peak was significantly slow.Besides,PQ peak fell more obviously than that in the control group and it was about 50% of the control group (μg/L:123.50 ± 11.67 vs.255.18 ± 12.29 in blood from hepatic portal veins,122.35± 11.72 vs.250.86± 11.15 in blood from peripheral veins).After 8 hours it fell much more quickly than that of the control group.After exposure to PQ for 48 hours,PQ concentration in the plasma was still lower than that of the control group (μg/L:0.53 ± 0.18 vs.15.98 ± 5.58 in blood from hepatic portal veins,0.31 ± 0.01 vs.15.03 ± 4.82 in blood from peripheral veins,both P < 0.01).With the toxicokinetics analysis,compared with the control group,the maximum concentration (Cmax) and area under the curve (AUC) of PQ in the plasma of hepatic portal veins and peripheral veins in the experimental group were significantly decreased [Cmax (μg/L):125.07 ± 9.49 vs.255.18 ± 12.29 in blood from hepatic portal veins,123.38 ± 9.52 vs.250.86 ± 11.15 in blood from peripheral veins;AUC (mg· L-1· h-1):1.6±0.2vs.3.3 ± 0.4 in blood from hepatic portal veins,1.5 ± 0.2 vs.3.2 ± 0.3 in blood from peripheral veins],time to the peak (Tmax) of PQ was slowed (hours:5.3 ± 1.9 vs.4.0 ± 0.0 in blood from hepatic portal veins,4.7 ± 1.5 vs.4.0 ± 0.0 in blood from peripheral veins),and PQ plasma half-life (t1/2) and mean retention time (MRT) were significantly shortened [t1/2 (hours):3.8 ± 1.2 vs.15.4± 3.7 in blood from hepatic portal veins,3.5 ± 1.0 vs.15.5 ± 2.7 in blood from peripheral veins;MRT (hours):8.0± 1.5 vs.13.4± 1.2 in blood from hepatic portal veins,7.6± 1.3 vs.13.3± 1.2 in blood from peripheral veins;all P < 0.01].After exposure to PQ,HR and RR in both the experimental group and the control group increased and reached to the peak about the 4th day and then the increase rate began to slow down gradually;SpO2slowed down gradually and reached to the valley about the 4th day and then it began to recover,but the change range of vital signs in the experimental group was smaller than that of the control group,and the parameters were significantly better than those of control group [4-day HR (bpm):134.50±3.00 vs.142.00±6.43,4-day RR (times/min):31.00±0.58 vs.34.33±0.94,4-day SpO2:0.900±0.006 vs.0.873±0.005,all P < 0.05].Conclusion Activated charcoal administrated at 30 minutes after PQ poisoning can slow down the increase rate of PQ concentration in the plasma,decrease the peak concentration and has less influence on vital signs in beagles.
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