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血液灌流對(duì)急性溴敵隆中毒體內(nèi)毒物清除效果的臨床研究和實(shí)驗(yàn)研究

發(fā)布時(shí)間:2018-06-10 07:32

  本文選題:溴敵隆中毒 + 血液灌流; 參考:《安徽醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:1.評(píng)價(jià)血液灌流(Hemoperfusion,HP)在急性溴敵隆(Bromadiolone)中毒患者和染毒犬體內(nèi)毒物的清除作用;2.比較活性炭罐和樹脂炭的毒物清除作用的優(yōu)劣。方法:1.測(cè)定生物樣品中溴敵隆含量的HPLC方法:實(shí)驗(yàn)采用3200型液相色譜-串聯(lián)質(zhì)譜儀,色譜條件及質(zhì)譜條件符合實(shí)驗(yàn)檢測(cè)標(biāo)準(zhǔn),參照溴敵隆毒檢標(biāo)準(zhǔn)檢測(cè)方法。2.溴敵隆中毒HP治療的臨床研究:回顧性分析溴敵隆中毒患者臨床病例資料。收集解放軍307醫(yī)院的病例,實(shí)驗(yàn)入組條件為所有溴敵隆中毒患者入院后同意接受HP并留取血樣本送檢,初步篩選后有21例病例納入本研究,分析21例行HP(活性炭罐)治療的急性溴敵隆中毒患者的臨床資料,比較每次灌流前后血液中溴敵隆濃度變化,觀察其單次清除率和總清除率,評(píng)價(jià)HP的治療效果。3.溴敵隆染毒比格犬模型的建立:將3只比格犬隨機(jī)編號(hào)(體重9-11kg),分別給予150mg、50mg、10mg劑量溴敵隆溶液經(jīng)腹腔注射染毒。觀察比格犬的癥狀表現(xiàn),并采集1d、2d、3d、4d、5d、6d外周靜脈血進(jìn)行毒物檢測(cè)。4.活性炭和樹脂血液灌流救治溴敵隆染毒比格犬的對(duì)比研究:將15只比格犬(體重9-11kg)隨機(jī)分為對(duì)照組(僅溴敵隆染毒)、實(shí)驗(yàn)組1(溴敵隆染毒后6h予活性炭HP)及實(shí)驗(yàn)組2(溴敵隆染毒后6h予樹脂HP)三組,每組5只,全部比格犬采用溴敵隆4.5mg/kg腹腔注射染毒。染毒后0.5h、2h、4h、6h、8h、12h、24h、30h于外周靜脈取血檢測(cè)血漿中溴敵隆濃度,觀察溴敵隆的濃度變化,評(píng)價(jià)HP的清除毒物效果。結(jié)果:1.測(cè)定生物樣品中溴敵隆含量的高效液相色譜法的建立發(fā)現(xiàn)血清中溴敵隆200ng/ml標(biāo)準(zhǔn)品質(zhì)譜圖中樣本溴敵隆出峰時(shí)間是5.4min,靈敏度、準(zhǔn)確度、精密度均能滿足實(shí)驗(yàn)要求,可以用于本實(shí)驗(yàn)研究。2.臨床研究21例急性溴敵隆中毒患者的臨床癥狀均有不同程度的改善,治療前后血液中溴敵隆濃度有明顯變化(p0.01),隨著hp次數(shù)增加,對(duì)毒物的總清除率提高更顯著(p0.01),且單次hp對(duì)溴敵隆清除率可高達(dá)30%以上。3.動(dòng)物實(shí)驗(yàn)研究:根據(jù)文獻(xiàn)記錄,分別對(duì)三只比格犬進(jìn)行不同劑量染毒,結(jié)果顯示,大劑量染毒犬(150mg)經(jīng)染毒后,2小時(shí)后出現(xiàn)精神萎靡,24小時(shí)后開始出現(xiàn)牙齦出血,并有少量便血,并3天后死亡,而小劑量染毒犬(10mg)經(jīng)染毒后,無明顯異常表現(xiàn)。而中劑量染毒犬(50mg)經(jīng)染毒后,出現(xiàn)便血,但無死亡現(xiàn)象,因此,確定50mg(4.5mg/kg)為本動(dòng)物實(shí)驗(yàn)研究的染毒劑量。4.活性炭和樹脂的毒物清除作用比較:實(shí)驗(yàn)結(jié)果顯示,hp能明顯加快比格犬體內(nèi)溴敵隆的清除,在檢測(cè)各個(gè)時(shí)間點(diǎn)上,三組清除率比較具有顯著統(tǒng)計(jì)學(xué)差異,其中以實(shí)驗(yàn)組2清除率最大(p0.05)。各組血漿溴敵隆濃度數(shù)據(jù)經(jīng)統(tǒng)計(jì)后得到各組毒物代謝動(dòng)力學(xué)參數(shù),結(jié)果顯示,三組消除半衰期具有統(tǒng)計(jì)學(xué)差異(170hvs.90hvs.43h,p0.05),且清除率三組相比也具有統(tǒng)計(jì)學(xué)差異(66.58ml/hvs.225.0ml/hvs.493.3ml/h,p0.05),溴敵隆時(shí)間-濃度曲線下面積(areaundercurve,auc)組間比較差異顯著(663790h*ng/mlvs.356830h*ng/mlvs.137910h*ng/ml,p0.05),而峰濃度(maximumconcentration,cmax)及平均保留時(shí)間(meanretentiontime,mrt)無明顯統(tǒng)計(jì)學(xué)差異(p0.05)。從實(shí)驗(yàn)結(jié)果來看,實(shí)驗(yàn)組2對(duì)溴敵隆清除效果最好。結(jié)論:1.hp能有效降低溴敵隆中毒患者(或染毒動(dòng)物)血液溴敵隆濃度,單次hp對(duì)溴敵隆清除率可高達(dá)30%以上,反復(fù)hp可顯著提高總體毒物清除率。且不良反應(yīng)少,從而能明顯縮短病程,減少再次出血等并發(fā)癥的發(fā)生。2.活性炭罐和樹脂罐均可有效清除體內(nèi)溴敵隆,但樹脂罐效果更優(yōu)。提示:急性溴敵隆中毒早期除進(jìn)行胃腸道內(nèi)毒物清除外應(yīng)盡早行hp治療,條件允許時(shí)優(yōu)選樹脂罐。
[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.
【學(xué)位授予單位】:安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R595.4

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