多次活性炭灌胃对大鼠血浆敌敌畏浓度的影响

目的 探讨活性炭灌胃对急性有机磷农药中毒的治疗作用.方法 30只雄性清洁级Wistar大鼠随机(随机数字法)分成3组:对照组(A组)、单次活性炭番泻叶组(B组)和多次活性炭番泻叶组(C组),每组10只.A组按35 mg/kg剂量经口敌敌畏染毒,不给予活性炭和番泻叶.B组按35 mg/kg剂量经口敌敌畏染毒,染毒后立即给予活性炭175 mg/kg,半小时后再予番泻叶35 mg/kg经口灌服.C组按35 mg/kg剂量经口敌敌畏染毒,染毒后立即给予活件炭175 mg/kg、番泻叶35 mg/kg每4 h经口灌服.每组均于染毒后不同时间分别采血,检测血中敌敌畏浓度和全血胆碱酯酶活性.对3组各时间点血中敌敌畏质最浓度、峰浓度(Cmax)、曲线下面积(AUC)0→∞、平均保留时间(MRT)值、胆碱酯酶活性数据进行单因素方差分析.结果 染毒后单次灌胃组及多次灌胃组血液中敌敌畏浓度水平显著低于对照组(P<0.05);染毒4 h后多次灌胃组血中敌敌畏浓度水平与单次灌胃组间差异具有统计学意义(P<0.05);活性炭灌胃两组的AUC,Cmax与对照组比较差异具有统计学意义(P<0.05).MRT三组比较差异无统计学意义(P>0.05).全血胆碱酯酶抑制水平于染毒后4 h内,B组、C组与A组比较差异具有统计学意义(P<0.05),B组与C组比较差异无统计学意义(P>0.05);4 h后,三组之间两两比较差异具有统计学意义(P<0.05).结论 染毒后多次灌胃组及单次灌胃组的峰浓度降低,进入血液的敌敌畏量减少,全血胆碱酯酶抑制水平得到改善,并且多次灌胃组疗效优于单次灌胃组.     

多次活性炭灌胃对大鼠血浆敌敌畏浓度的影响

Objective To assess the therapeutic effects of activated charcoal on the acute dichlorvos poisoning in rats. Method Thirty male clean grade Wistar rats were randomly (random number) divided into three groups: control group (group A, n = 10), single dose activated charcoal group (group B, n = 10) and multi-dose activated charcoal (group C, n=10). The rats of group A were suffered from 35 mg/kg dichlorvos exposure by oral without activated charcoal and senna. The rats of group B received 35 mg/kg dichlorvos exposure by oral with 175 mg/kg activated charcoal given immediately after dichlorvos exposure and 35 mg/kg senna given half an hour later. In the group C, 35 mg/kg dichlorvos was given to rats by oral with 175 mg/kg activated charcoal given immediately after dichlorvos exposure and 35 mg/kg senna given half an hour later and then every four hours. Blood samples were collected from the carotid artery at different intervals after exposure. DDVP concentration and total blood acetyl-cholinesterase activity were detected. Differences in serum DDVP concentration, Cmax, AUC (0→∞ ), MRT and acetylcholinesterase among three groups were calculated by using ANOVA. Results Serum DDVP levels in single dose group and in multi-dose group were significantly different from those in control group (P < 0.05). The DDVP levels in multi-dose group were significantly different from those in single dose group 4 hours after exposure (P < 0.05). The AUC and Cmax in activated charcoal treatment groups were significantly different from those in control group (P < 0.05). There were no significant differences in MRT among three groups. Fours hours after exposure to dichlorvos,the levels of serum acetylcholinesterase in rats of group B and group C were significantly different from that in rats of group A (P < 0.05), and there was no significant difference in acetylcholinesteras between group B and group C (P > 0.05). Another four hours later, no differences in acetylcholinesterase were found a-mong three groups (P > 0.05). Conclusions The peak concentrations of dichlorvos in blood are lower in group B and group C, and the blood acetylcholinesterase inhibition is quelled by activated charcoal. Therefore, the effects of multi - dose of activated charcoal is better than that of single dose of activated charcoal.     

活性炭血液灌流对有机磷农药敌敌畏和解毒药阿托品的作用

目的评估活性炭血液灌流对有机磷农药敌敌畏和解毒药阿托品的作用。方法在人血样(由解放军307医院血库提供的正常人血样)中加入敌敌畏和阿托品后,分成空白对照组和血液灌流组,观察灌流前后血中敌敌畏浓度和阿托品浓度以及血清中胆碱酯酶活力的变化。结果活性炭血液灌流中敌敌畏和阿托品的吸附率分别为(0.98±0.05)%和(0.68±0.01)%。在混合吸附试验中,吸附后的阿托品和敌敌畏之比较吸附前浓度之比增加。同时,吸附后假性胆碱酯酶活力比吸附前增长了近3倍。结论虽然在体外人血中活性炭血液灌流对人血中敌敌畏的吸附率较低(与空白组比较,P>0.05),但大大提高了血清中胆碱酯酶活力,同时提高了血中阿托品和敌敌畏的浓度之比,从而更易到达阿托品化。     

急性敌敌畏中毒大鼠的早期心肌损伤

目的 研究急性敌敌畏(dichlorvos,DDVP)中毒导致的早期心肌损伤表现.方法 Sprague Dawley(SD)大鼠24只,随机(随机数字法)分成对照组和中毒组两组,每组12只.采用右侧颈动脉置管术动态监测有创血流动力学指标;测定血清肌钙蛋白T(cardiac troponin T,CTnT)和心房利钠肽(brain natriuretic peptide,BNP)水平;观察心肌组织病理学改变.结果 ①中毒组自身前后对照:中毒1 h内,心率(heart rate,HR)和室内压上升段最大变化率(maximum ascending rates of left ventricular pressure,+dp/dtmax)均有显著下降;室内压下降段最大变化率(maximum descending rates of left ventricular pressure,-dp/dtmax),左室舒张末压(1eft ventricular end diastolic pressure,LVEDP)有显著升高(P＜0.01).其中均以7 min时改变最显著.②中毒组与对照组比,血清CTnT值显著升高(P＜0.01),血清BNP值差异无统计学意义(P＞0.05).③中毒组心肌HE染色存在病理学损害.结论 急性有机磷中毒(acute organophosphorus pesticides poisoning,AOPP)其早期可导致大鼠心肌损伤,血流动力学紊乱,心功能受抑.CTnT可作为早期评价AOPP心肌损伤的指标,而BNP在AOPP诊治中的意义不大.

Abstract：

Objective To investigate the myocardial injury in the early stage of acute dichlorvos poisoning in rats. Method A total of 24 Sprague Dawley rats were randomly (random number) divided into control group(n = 12) and poisoning group(n = 12). Hemodynamic variables were monitored by using an arterial cannula inserted into right arteria carotis communis. Serum levels of cardiac troponin T(CTnT) and brain natriuretic peptide (BNP) were measured. Myocardial tissue was observed with HE stain under microscope. Results The rats of poisoning group showed that the heart rate (HR) and maximum ascending rates of left ventricular pressure(+ dp/dtmax)were significant decreased in an hour after poisoning (P ＜0.01). The maximum descending rates of left ventricular pressure(-dp/dtmax)and left ventricular end diastolic pressure (LVEDP)were markedly increased (P＜0. 01) and reached peak in 7 minutes in the poisoning group. Compared with the control group, cardiac troponin T obviously changed in rats poisoned with dichlorvos in the first hour. BNP was not affected after poisoning(P ＞ 0. 05). Myocardial damage was found in the poisoning rats.Conclusions Myocardial injury and heart failure occurred in the early stage of acute organophosphorus pesticides poisoning(AOPP) in rats. CTnT could play a major role in AOPP while BNP might not be involved in.     

LC-MS/MS法测定人血浆中丙戊酸的浓度

目的建立快速、灵敏的液相色谱-串联质谱(LC-MS/MS)法测定人血浆中丙戊酸的浓度。方法采用乙腈沉淀蛋白法处理人血浆样本,选用Shimpack VP-ODS色谱柱(150mm×2.0mm I.D,5μm),以甲醇:5mmol/L乙酸铵(55∶45,v/v)为流动相,流速为0.4mL/min,采用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,负离子方式,选择监测离子反应分别为m/z 142.9→m/z 142.9(丙戊酸)和m/z 179.0→m/z 179.0(1-庚烷磺酸)。结果丙戊酸和内标1-庚烷磺酸的保留时间分别为3.03、2.38min;血浆中丙戊酸的线性范围为0.800~80.0μg/mL(r0.99),定量下限为0.800μg/mL;批内、批间精密度(RSD)均小于15%;准确度(RE)均在±15%的范围以内;平均提取回收率为(84.1±2.4)%;平均基质效应因子为(104.3±2.0)%。稳定性试验中,在各种贮存条件下的血浆中,丙戊酸均较稳定。结论该方法适用于人血浆中丙戊酸浓度的测定及丙戊酸半钠缓释片的人体药代动力学研究。     

测定血液病患者血浆Venetoclax浓度的HPLC-MS/MS方法

目的 建立测定血液病患者血浆Venetoclax浓度的HPLC-MS/MS法.方法 患者血浆经甲醇(含内标Venetoclax-d8)沉淀蛋白处理.色谱柱为Ultimate@XB-C18(4.6×50 mm,5μm),柱温60℃.流动相为含0.1％甲酸和2 mmol·L1乙酸铵的水溶液和含0.1％甲酸的甲醇溶液,流速0...     

人血浆中头孢地尼浓度的HPLC测定法及药物动力学研究

目的 建立测定头孢地尼(Cefdinir Capsules)在人体血浆中浓度的高效液相色谱(HPLC)法并计算药动学参数.方法 18名健康志愿者单剂量口服头孢地尼胶囊500mg,肘静脉取血少量,并分取血浆,用甲醇沉淀血浆蛋白质,采用Hypersil ODS色谱柱(250 mm×4.6 mm.5 μm),以乙腈-水-冰乙醋-三乙胺(10∶90∶0.14∶0.16)作为流动相进行分离,检测波长265 nm,流速为1.0 ml/min.结果 受试制剂和参比制剂中头孢地尼主要药动学参数:达峰时间tmax为1.05±0.12 h和1.05±0.12 h,峰浓度为Cmax14.26±2.11μg/ml和14.13±2.11 μg/ml,消除相半衰期t1/2为1.71±0.60 h,曲线下面积(AUC)0～∞为23.41±3.35 μg·h/ml和23.14±2.92 μg·h/ml.结论 该方法简便、准确、重现性好,适合头孢地尼的血药浓度测定.受试制剂和参比制剂生物等效.     

血液灌流对急性草乌中毒兔血浆毒性成分及组织病理学的影响

目的 探讨血液灌流对急性草乌中毒兔血浆毒性成分和组织病理学的影响.方法 雄性日本大耳白兔16只,随机分成中毒组(AP组,n=8)和血液灌流治疗组(AH组,n=8).两组用草乌酒1 mL/kg灌胃,制作急性中毒模型(以1 h内出现心律失常为制模成功标准),AH组用活性碳血液灌流2 h.光镜下观察两组兔脑、心肌、肝组织病理改变.分别比较两组相同时间点血浆中乌头碱、新乌头碱、次乌头碱浓度.两样本均数比较采用成纽t检验.结果 AP组兔脑组织、心肌组织、肝组织充血水肿明显,AH组兔的肝脏组织轻度允血,脑组织、心肌组织未见明显改变;两组染毒后1 h内血浆乌头碱、新乌头碱、次乌头碱浓度比较,差异无统计学意义(P＞0.05).AH组染毒后2 h,3 h血浆乌头碱、新乌头碱、次乌头碱浓度分别为[(2.11±1.08),(2.02±1.46)],[(39.70±9.31),(19.71±16.06)],[(1.70±0.71),(2.12±1.33)]ng/mL,均明显低于AP组,差异有统计学意义(P＜0.05).结论 急性草乌中毒兔血液灌流治疗后血浆中草乌成分浓度明显降低,器官组织病理改变减轻,血液灌流是兔急性草乌中毒的有效治疗手段.     

液相色谱串联质谱测定大鼠血浆中多黏菌素E甲磺酸钠及多黏菌素E方法的建立及应用

目的 建立液相色谱串联质谱（LC-MS/MS）法测定大鼠血浆中多黏菌素E甲磺酸钠（CMS）及其活性成分多黏菌素E并进行应用。方法 通过多黏菌素E主成分E1及E2浓度之和间接得到多黏菌素E的浓度。在大鼠血浆样品中加入硫酸对CMS进行水解，通过测定水解后与水解前血浆样品中多黏菌素E的浓度差间接测定CMS浓度。采用固相萃取法对样品进行预处理。色谱柱选择Phonomenex Kinetex XB-C18柱，质谱采用电喷雾电离源（ESI源）及多反应监测（multi-reaction monitoring,MRM）模式。其中待测物质多黏菌素E1、多黏菌素E2、内标多黏菌素B1的离子通道分别为m/z390.7→101.3、m/z 386.0→101.2、m/z 402.3→101.2。结果 多黏菌素E1及E2的测定不受大鼠血浆中内源物质的影响，且分别在0.187～6.24 mg/L、0.037 0～1.23 mg/L内线性良好，批内与批间精密度良好，变异系数均<15%。多黏菌素E1、E2准确度范围分别为100.1%～113.3%和94.9%～107.3%。多黏菌素E1、E2的提取回收率分别为2...     

Protective effects of Y-27632 on acute dichlorvos poisoning in rats

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase–MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.     

活性炭对急性毒鼠强中毒家兔的疗效研究

目的探讨口服活性炭对急性毒鼠强中毒家兔的治疗作用。方法将33只家兔随机分为6组：A组,低剂量染毒未治疗;B组,低剂量染毒早期治疗;C组,低剂量染毒延迟治疗;D组,致死剂量染毒未治疗;E组,致死剂量染毒治疗;F组,二甲基亚砜。每组家兔给予相应处理后定时采集血液和粪便,使用气相色谱一氮磷检测器法测定血浆毒鼠强浓度和粪便毒鼠强含量,并进行毒鼠强代谢动力学分析,同时观察家兔中毒表现。结果A组、B组、C组3组间毒鼠强血浆浓度和所有代谢动力学参数都有显著性差异,其中B、C两组的排泄半衰期(Tke1/2)仅相当于A组的一半,其清除率则分别较A组提高了3倍和2倍以上,曲线下面积(AUC)却分别只有A组的29．8％和45．9％;B、C两组在染毒后最初3d收集的粪便中毒鼠强含量明显高于A组。在致死剂量染毒组中,D组的死亡、肢体瘫痪、惊厥发生率均明显高于E组。结论口服活性炭可以明显减少毒鼠强在家兔体内的吸收,加快毒鼠强从家兔体内排出,从而减轻中毒症状,降低死亡率。     

Repetitive doses of activated charcoal in the treatment of poisoning

Activated charcoal has found a renewed role in the management of overdosed patients. Routinely administered to reduce the gastrointestinal (GI) absorption of many drugs, growing evidence indicates that repeated doses of charcoal also may enhance drug elimination. Some drugs are excreted into the bile or gastric fluids (phencyclidine, digoxin) and are reabsorbed. Other drugs (theophylline, phenobarbital) can diffuse from the plasma into the lumen of the GI tract. Activated charcoal is administered at regular intervals to sequester these toxins in the GI tract, eventually causing their excretion in feces. This article reviews the evidence for the safety and efficacy of repetitive charcoal therapy. While supportive management remains the mainstay of therapy in poisoned patients, activated charcoal is inexpensive, effective, simple to administer, and may obviate the need for more invasive methods of toxin removal.     

急性毒鼠强中毒小鼠的实验性药物治疗研究

目的研究二巯基丙磺酸钠(Na-DMPS)及维生素B6(VB6)对急性毒鼠强中毒小鼠的治疗作用.方法用析因设计的方法,以惊厥潜伏期及生存时间为观察指标,观察二巯基丙磺酸钠及维生素B6对急性毒鼠强中毒小鼠的治疗作用.结果二巯基丙磺酸钠及维生素B6在早期可明显延长惊厥的潜伏期,延长动物的生存时间.结论二巯基丙磺酸钠及维生素B6对毒鼠强中毒小鼠有治疗作用,可辅以镇静药物提高救治的成功率.     

活性炭和甘露醇联合应用对急性有机磷农药中毒的疗效

目的 探讨口服活性炭和甘露醇对急性有机磷农药中毒(AOPP)的毒物清除作用.方法 2004年1月至2009年12月南昌大学第一附属医院收治的41例重症AOPP患者随机分为试验组(活性炭吸附毒物和甘露醇导泻治疗组,n=21)和对照组(未用活性炭吸附毒物和甘露醇导泻治疗组,n=20).两组患者均进行AOPP急救常规治疗,观察两组患者阿托品化时间、抢救成功率和住院时间的差异.结果 试验组阿托品化时间、抢救成功率和住院时间与对照组比较差异[(3.60±1.6)h vs.(17.5±13.4)h;(4.1±1.45)d vs.(8.00±2.13)d;100% vs.(70.0±4.7)]均有统计学意义(P＜0.01).结论 活性炭和甘露醇联合应用较传统洗胃法更能有效清除进入体内的有机磷农药,且能缩短患者阿托品化时间和住院时间,进一步提高AOPP的抢救成功率,改善患者预后.