血液灌流对急性溴敌隆中毒体内毒物清除效果的临床研究和实验研究

发布时间：2018-06-10 07:32

本文选题：溴敌隆中毒 + 血液灌流　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:1.评价血液灌流(Hemoperfusion,HP)在急性溴敌隆(Bromadiolone)中毒患者和染毒犬体内毒物的清除作用;2.比较活性炭罐和树脂炭的毒物清除作用的优劣。方法:1.测定生物样品中溴敌隆含量的HPLC方法:实验采用3200型液相色谱-串联质谱仪,色谱条件及质谱条件符合实验检测标准,参照溴敌隆毒检标准检测方法。2.溴敌隆中毒HP治疗的临床研究:回顾性分析溴敌隆中毒患者临床病例资料。收集解放军307医院的病例,实验入组条件为所有溴敌隆中毒患者入院后同意接受HP并留取血样本送检,初步筛选后有21例病例纳入本研究,分析21例行HP(活性炭罐)治疗的急性溴敌隆中毒患者的临床资料,比较每次灌流前后血液中溴敌隆浓度变化,观察其单次清除率和总清除率,评价HP的治疗效果。3.溴敌隆染毒比格犬模型的建立:将3只比格犬随机编号(体重9-11kg),分别给予150mg、50mg、10mg剂量溴敌隆溶液经腹腔注射染毒。观察比格犬的症状表现,并采集1d、2d、3d、4d、5d、6d外周静脉血进行毒物检测。4.活性炭和树脂血液灌流救治溴敌隆染毒比格犬的对比研究:将15只比格犬(体重9-11kg)随机分为对照组(仅溴敌隆染毒)、实验组1(溴敌隆染毒后6h予活性炭HP)及实验组2(溴敌隆染毒后6h予树脂HP)三组,每组5只,全部比格犬采用溴敌隆4.5mg/kg腹腔注射染毒。染毒后0.5h、2h、4h、6h、8h、12h、24h、30h于外周静脉取血检测血浆中溴敌隆浓度,观察溴敌隆的浓度变化,评价HP的清除毒物效果。结果:1.测定生物样品中溴敌隆含量的高效液相色谱法的建立发现血清中溴敌隆200ng/ml标准品质谱图中样本溴敌隆出峰时间是5.4min,灵敏度、准确度、精密度均能满足实验要求,可以用于本实验研究。2.临床研究21例急性溴敌隆中毒患者的临床症状均有不同程度的改善,治疗前后血液中溴敌隆浓度有明显变化(p0.01),随着hp次数增加,对毒物的总清除率提高更显著(p0.01),且单次hp对溴敌隆清除率可高达30%以上。3.动物实验研究:根据文献记录,分别对三只比格犬进行不同剂量染毒,结果显示,大剂量染毒犬(150mg)经染毒后,2小时后出现精神萎靡,24小时后开始出现牙龈出血,并有少量便血,并3天后死亡,而小剂量染毒犬(10mg)经染毒后,无明显异常表现。而中剂量染毒犬(50mg)经染毒后,出现便血,但无死亡现象,因此,确定50mg(4.5mg/kg)为本动物实验研究的染毒剂量。4.活性炭和树脂的毒物清除作用比较:实验结果显示,hp能明显加快比格犬体内溴敌隆的清除,在检测各个时间点上,三组清除率比较具有显著统计学差异,其中以实验组2清除率最大(p0.05)。各组血浆溴敌隆浓度数据经统计后得到各组毒物代谢动力学参数,结果显示,三组消除半衰期具有统计学差异(170hvs.90hvs.43h,p0.05),且清除率三组相比也具有统计学差异(66.58ml/hvs.225.0ml/hvs.493.3ml/h,p0.05),溴敌隆时间-浓度曲线下面积(areaundercurve,auc)组间比较差异显著(663790h*ng/mlvs.356830h*ng/mlvs.137910h*ng/ml,p0.05),而峰浓度(maximumconcentration,cmax)及平均保留时间(meanretentiontime,mrt)无明显统计学差异(p0.05)。从实验结果来看,实验组2对溴敌隆清除效果最好。结论:1.hp能有效降低溴敌隆中毒患者(或染毒动物)血液溴敌隆浓度,单次hp对溴敌隆清除率可高达30%以上,反复hp可显著提高总体毒物清除率。且不良反应少,从而能明显缩短病程,减少再次出血等并发症的发生。2.活性炭罐和树脂罐均可有效清除体内溴敌隆,但树脂罐效果更优。提示:急性溴敌隆中毒早期除进行胃肠道内毒物清除外应尽早行hp治疗,条件允许时优选树脂罐。
[Abstract]:Objective: 1. to evaluate the scavenging effect of Hemoperfusion (HP) in acute brobrochyon (Bromadiolone) poisoning patients and infected dogs; 2. to compare the advantages and disadvantages of the active carbon cans and resin charcoal. Method: 1. to determine the HPLC method for bromate content in biological samples: the experiment adopts the 3200 type liquid chromatography tandem mass spectrometer, The chromatographic conditions and mass spectrum conditions conform to the experimental test standard. A clinical study on the treatment of.2. with the standard detection method of the gppl poisoning: a retrospective analysis of the data of the clinical case of the patients with the intoxication of the paladin. The cases of the PLA 307 Hospital were collected. The condition of the experimental group was that all the patients with the intoxication of the group agreed to accept HP after admission to the hospital. 21 cases were included in this study after primary screening. The clinical data of 21 patients with acute chlorino poisoning treated by HP (activated charcoal tank) were analyzed, and the changes of the concentration of chlorino in blood were compared before and after each perfusion. The single clearance rate and total clearance rate were observed, and the therapeutic effect of HP was evaluated by.3.. Establishment: 3 beagle dogs were numbered randomly (weight 9-11kg), and were injected with 150mg, 50mg, and 10mg, respectively, to observe the symptoms of Beagle, and to collect 1D, 2D, 3D, 4D, 5D, 6D peripheral venous blood for poison detection of.4. activated carbon and tree fat hemoperfusion for the treatment of Beagle beagle dogs: 15 Only the Beagle (body weight 9-11kg) was randomly divided into the control group (9-11kg), the experimental group (6h to active charcoal HP) and the experimental group 2 (6h to the resin HP) in the experimental group, three groups of 5 rats in each group. All the Beagle dogs were injected with the intraperitoneal injection of the HP, 2h, 4h, 6h, 8h, 12h, The concentration of brobrom in plasma was observed and the concentration of brobrom was observed and the effect of HP was evaluated. Results: 1. the determination of bromate content in biological samples was established by high performance liquid chromatography (HPLC). It was found that the peak time of brobrom 200ng/ml standard mass spectrometry in serum was 5.4min, sensitivity, accuracy and precision could be satisfied. The clinical symptoms of 21 cases of.2. clinical study can be improved to varying degrees. There is a significant change in the concentration of the blood in the blood before and after the treatment (P0.01). As the number of HP increases, the total clearance of the poison is increased more (P0.01), and the clearance rate of the single HP to the group is up to 30%. The above.3. animal experiment study: according to the literature records, three beagle dogs were poisoned in different doses. The results showed that after 2 hours, a large dose of infected dog (150mg) was mentally depressed, and gingival bleeding began to appear after 24 hours, and a small amount of blood, and 3 days later, died, and the small dose of 10mg was not obvious. Abnormal performance. While the medium dose poisoned dog (50mg) was infected, there was no death phenomenon. Therefore, 50mg (4.5mg/kg) was determined to compare the toxic effect of.4. activated carbon and resin. The experimental results showed that HP could significantly increase the clearance of chmodine in the Beagle dog, at all time points, The clearance rate of the three groups was significantly different, among which the 2 clearance rate was the largest in the experimental group (P0.05). The data of the concentration of the group were obtained. The results showed that the half-life of the three groups was statistically different (170hvs.90hvs.43h, P0.05), and the clearance rate was also statistically significant in the three groups. The difference (66.58ml/hvs.225.0ml/hvs.493.3ml/h, P0.05) and the area of areaundercurve (AUC) under the time concentration curve were significantly different (663790h*ng/mlvs.356830h*ng/mlvs.137910h*ng/ml, P0.05), while the peak concentration (maximumconcentration, Cmax) and the average retention time (meanretentiontime, MRT) had no significant statistical difference (P0.05). From the experimental results, the results of the experimental group 2 have the best effect on the clearance of the palmate. Conclusion: 1.hp can effectively reduce the concentration of the blood in the blood of the patients (or infected animals), and the scavenging rate of the single HP can be as high as more than 30%. Repeated HP can significantly increase the total poison clearance rate, and the adverse reaction is less, thus the course of the disease can be shortened and the reactivity can be reduced. .2. activated carbon cans and resin cans can effectively clear the body of the body, but the effect of the resin can is better. It is suggested that early HP treatment should be done in the early stage of acute pochon poisoning except for the removal of poison in the gastrointestinal tract.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R595.4

【参考文献】