敌敌畏对大鼠脑组织N-甲基-D-天门冬氨酸受体活性的影响

目的 研究敌敌畏(DDVP)染毒后大鼠脑组织中N-甲基-D-天门冬氨酸(NMDA)受体的变化规律,探讨其在有机磷农药中毒中的作用。方法 55只雄性SD大鼠分为11组,每组5只,一组为生理盐水(NS)组,高剂量组(25mg/kg)和低剂量组(15mg/kg)各5组,染毒组分别以敌敌畏腹腔注射,染毒后4h、8h、16h、24h、48h处死,测定大鼠全血和脑组织的乙酰胆碱酯酶(AChE)活性以及脑组织中NMDA受体的活性。结果 DDVP染毒后大鼠全血和脑组织的AChE活性显著下降,且脑组织AChE活性下降更多,抑制率大于80％,恢复更迟缓。脑组织中NMDA受体的最大结合容量(Bmax)在4h便明显下降,于24h达到最低,然后逐渐升高,受体的平衡解离常数(Kd)在4h时明显上升,于24h达到最高,然后逐渐下降。结论 DDVP染毒对大鼠脑组织AChE活性抑制严重,说明中枢神经系统对DDVP的毒作用敏感。同时DDVP染毒对大鼠脑组织中NMDA受体产生下降调节,表现为受体数量减少、亲和力降低。推测这是机体的一种自身调节机制,可减少过度刺激并保护中枢神经系统。     

乐果90 d染毒对大鼠大脑皮质GABA系统的影响

[目的]研究乐果[O,O-二甲基-S-(N-甲基氨基甲酰甲基)二硫化磷酸酯]90d染毒对大鼠大脑皮质γ-氨基丁酸(GABA)系统的影响。[方法]48只健康雄性SD大鼠分成4组,剂量分别为O(生理盐水)、5、10、20mg/kg,灌胃给药,每周染毒5d(次),实验周期90d,每天称重1次,每3天记录动物饲料消耗量,定期测定全血乙酰胆碱酯酶(AChE)活性,实验结束时全部动物断头处死,测定延髓AChE活性,反相高效液相色谱荧光法测定大脑皮质GABA含量,放射性配体受体结合法测定大脑皮质GABA_A受体的活性。[结果]实验期间,各染毒组动物全血AChE活性明显抑制,实验后期有所恢复。实验结束时,低、中、高染毒组延髓AChE活性分别约为对照组的78%、63%、42%。与对照组相比,中、高剂量组大脑皮质GABA含量明显降低(P<0.01);GABA_A受体的最大结合容量(maximum binding capacity,Bmax)低剂量组升高(P<0.05),中剂量组降低(P<0.05);各剂量组GABA_A受体的平衡解离常数(equilibrium dissociation constant,Kd)比对照组均有降低,但仅低、中剂量组差异有统计学意义(P<0.05)。[结论]乐果90d染毒过程中大脑皮质GABA含量、GABA_A受体功能都有所改变,可能参与了乐果慢性中毒过程中的非胆碱能机制。     

杀扑磷的毒性研究

目的　研究杀扑磷原药的急性和亚慢性毒性及致突变性 ,求出最大无作用剂量。方法　按照GB 15 670 -1995《农药登记毒理学试验方法》和GB 15 193 -94进行试验。结果　雌性大鼠LD50 为 3 8 3mg/kg ,雄性大鼠为 3 1 6mg/kg。小鼠骨髓多染红细胞微核试验和小鼠精子畸变试验均为阴性。大鼠亚慢性经口毒性试验显示 ,11 67mg/kg和 3 5 0 0mg/kg饲料组全血胆碱酯酶活力抑制明显 ,3 5 0 0mg/kg饲料组 ,雌性大鼠总摄食量明显减少。结论　杀扑磷的最大无作用剂量为 :雌性大鼠(1 2 6± 0 0 8)mg/ (kg·d) ,雄性大鼠 (0 40± 0 0 4)mg/ (kg·d)。     

甲胺磷与乙酰甲胺磷对乙酰胆碱酯酶毒效应的比较

目的　探讨高毒有机磷化合物甲胺磷及其替代品乙酰甲胺磷对乙酰胆碱酯酶 (AChE)的抑制作用及机制。方法　提取人红细胞膜及大鼠脑突触体膜后 ,体外实验中用Ellman法测定在不同受试物浓度、不同作用时间下剩余AChE活力 ;整体实验中用Ellman法测定不同脑区AChE活力。结果　乙酰甲胺磷和甲胺磷在体外对人红细胞膜及大鼠大脑皮层突触体膜AChE均有不可逆的抑制作用 ,且有明显的剂量 -效应和时间 -效应关系 ,两者对人红细胞膜及大鼠各脑区突触体膜AChE活力的半数抑制浓度 (IC50 )分别约为 1 0 - 4mol/L、1 0 - 5mol/L ,双分子速率常数 (Ki)分别为 1 0 2mol·L 1 ·min 1 、1 0 3mol·L 1 ·min 1 左右。在整体实验中 ,连续 5d给大鼠腹腔注射乙酰甲胺磷和甲胺磷 ,其全血AChE活力的抑制率逐渐上升 ,第 5天分别达到 68.2 4 %和 54 .80 %。乙酰甲胺磷仅对大鼠脑干AChE活力有抑制作用 (抑制率为 31 .68% ) ,其余脑区均未见明显影响 ;而甲胺磷对各脑区AChE活力均有较强的抑制 ,以小脑和脑干最强 ,分别为 71 .51 %和 61 .85 %。结论　乙酰甲胺磷和甲胺磷在体外对人红细胞膜和大鼠大脑皮层突触体膜AChE活力均有不同程度的抑制作用 ;在整体实验中对大鼠全血AChE活力均有抑制作用。对脑区AChE的抑制存在差异可能是两者毒     

美金刚对敌敌畏染毒大鼠脑组织NMDA受体的保护作用

目的　研究美金刚对敌敌畏染毒大鼠脑组织N 甲基 D 天冬氨酸 (NMDA)受体的保护作用及其治疗有机磷农药中毒的机制。方法　雄性SD大鼠用 2 5mg/kg敌敌畏染毒 ,再用美金刚 5、15、45mg/kg治疗 ,观察大鼠中毒症状出现强度与时间 ;染毒后 16h测定大鼠全血和脑组织乙酰胆碱酯酶 (AChE)活力及NMDA受体活性。结果　美金刚 15、45mg/kg治疗组大鼠中毒症状出现时间分别为 (18.40± 1.14 )、(2 1.40±1.52 )min ,较敌敌畏组 [(16.75± 1.62 )min]明显延长 ;肌颤强度分别为 1.60± 1.14、0 .80± 0 .84,较敌敌畏组(2 .85± 0 .3 7)明显减轻 ;症状总评分分别为 8.80± 1.79、9.0 0± 2 .2 4,较敌敌畏组 (14 .60± 1.70 )明显改善。美金刚对敌敌畏染毒大鼠全血和脑组织AChE活力均未见明显影响。敌敌畏染毒大鼠脑组织NMDA受体密度减少、亲和力下降 ,其Bmax和Kd值分别为 (0 .46± 0 .0 6)pmol/mgpro、(75.55± 7.87)nmol/L ,分别较阴性对照组 [(0 .62± 0 .0 4)pmol/mgpro、(3 7.3 7± 4.17)nmol/L]下降和上升。 5、15mg/kg美金刚可拮抗敌敌畏染毒对大鼠脑组织NMDA受体的影响 ,这两组的Bmax值分别为 (0 .55± 0 .0 7)、(0 .64± 0 .0 7)pmol/mgpro ,Kd值分别为 (3 8.68± 4.54)、(3 2 .58± 3 .90 )nmol/L。美金刚 45m     

喂饲三唑磷6个月对大鼠效应生物标志物的影响

[目的]探讨大鼠6个月摄入有机磷杀虫剂三唑磷(Hoe 02960)对效应生物标志物的影响.[方法]用含三唑磷0(对照组)、3、100mg/kg饲料喂饲SD大鼠连续6个月,3个剂量组每组动物20只,雌雄各半.于染毒前和染毒后第2、4、6、26周分别取大鼠的血液分析全血胆碱酯酶(BChE)、血浆胆碱酯酶(PChE)和红细胞胆碱酯酶(EChE)活性;于第26周分别取大鼠的尿和血,作尿和血常规及生化指标测定,同时进行动物肝、脾等脏器的病理检查.[结果]各剂量组大鼠6个月内均无死亡,体重增重、脏器系数均无明显差异.2周时100mg/kg剂量组BChE活性显著降低;4周时3、100mg/kg剂量组活性降低(P<0.05,P<0.01);6周时100mg/kg剂量组活性降低有显著性.各剂量组 BChE抑制率在第四周最高,雌鼠100 mg/kg抑制率达到21.8%,其他各剂量组抑制率均<20%,BChE活性在第六周开始逐渐回复,PChE情况与 BChE相似.各剂量组EChE抑制率随摄食时间增加而升高,至26周时 3、100 mg/kg 剂量组活性降低有显著性,3 mg/kg雄、雌大鼠抑制率分别为 5.6%和 6.0%;100 mg/kg雄、雌大鼠抑制率分别为10.6%和 11.4%,血液碱性磷酸酶(AKP)活性明显升高,RBC和Hb明显降低.病理组织学检查发现100 mg/kg剂量组肝脏肝细胞浊肿及空泡变性;脾有淤血、见色素沉着.[结论]BChE、PChE活性在喂饲早期(2～6周)可考虑作为三唑磷接触生物标志物;RBC、Hb和AKP活性在6个月接触三唑磷后可作为胆碱酯酶平行标志物;在6个月接触三唑磷过程中EChE活性虽有一定改变,但能否作为效应标志物,尚需作进一步跟踪确认.     

大鼠毒死蜱重复染毒后血清胆碱酯酶活性及其变化规律

目的了解毒死蜱(Chlorpyrifos,CPF)重复染毒后大鼠血清中乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)在不同时间点的活性情况,并分析两酶活性关系。方法将60只成年雌性SD大鼠按体重随机分成5组,每组12只,分别为毒死蜱组:2.50、5.00、10.00、20.00mg/kg及1个正常对照组。连续灌胃染毒10d,在第2、4、7和11d分别对部分动物(每次每组3只)收集血液样本,测定AChE、BuChE活性。结果血清中AChE、BuChE活性随着毒死蜱剂量、染毒时间增加而降低,呈现一定程度上的相关性。血清中AChE活性和BuChE活性呈现出正相关性(r=0.872,P0.01),随着重复染毒两酶变化趋势相同,但BuChE抑制程度更大(P0.01)。结论 10d重复染毒后AChE、BuChE抑制程度会增加。血清BuChE可考虑作为有机磷农药暴露的标志物。     

天麻对染铝大鼠胆碱能系统的影响

目的　探索天麻对染铝大鼠的胆碱能系统的影响。方法　健康成年雄性SD大鼠 36只 ,按体重随机分为 6组 ,即生理盐水组、Al3 + 5mg/kg 组、Al3 + 10mg/kg 组、生理盐水 +天麻组、Al3 + 5mg/kg+天麻组和Al3 + 10mg/kg+天麻组。Al为AlCl3 溶液 ,腹腔注射 ,0 2ml/d ,每连续注射 3d间歇 1d ,6 0d内注射 4 5次。所有动物饲以普通饲料 ,自由饮水和进食。加天麻组 ,以 0 4 g/kg 的剂量在饮水中加入天麻。结果　乙酰胆碱酯酶 (AChE)活力测定发现 ,Al3 + 5mg/kg 组和Al3 + 10mg/kg 组与生理盐水组相比 ,仅Al3 + 10mg/kg 组AChE活力明显降低 ,差异有显著性 (P <0 0 1)。Al3 + 10mg/kg+天麻组的AChE活力较Al3 + 10mg/kg 组明显增高 ,差异有显著性 (P <0 0 1) ,Al3 + 5mg/kg+天麻组与Al3 + 5mg/kg 组相比 ,AChE活力差异无显著性。结论　铝可以降低AChE的活力 ,同时天麻可以使染铝大鼠的AChE活力维持在正常水平。     

接触倍硫磷大鼠的视网膜变性

有机磷杀虫剂的急性、亚急性毒性实验中,观察到受试动物视网膜电图(ERG)a波和b波振幅降低。曾报道长期接触有机磷农药可使动物或人发生睫状肌和视神经变性。本文研究长期接触倍硫磷对大鼠视网膜的慢性毒作用。实验组为40只雄性有色大鼠和20只白色大鼠,体重约为150g。对照为20只雄性有色大鼠和15只雄性白色大鼠。皮下注射给药,每周两次,每次50mg/kg。为期一年的实验中,每鼠的总剂量为1.6～1.8g。实验过程中,视网膜电图每3个月检查一次,眼底每日检查一次,组织学检查每3个月一次,在第3个月     

平原和模拟高原条件下梭曼中毒对AChE活力影响的比较

采用DTNB显色法 ,研究平原和模拟 40 0 0m高原缺氧条件下梭曼对犬、大鼠组织及全血AChE活力的影响。结果显示 :(1)缺氧可抑制AChE活性。(2 )模拟高原条件下梭曼对两种动物AChE的抑制和平原条件下一样 ,均为持续性抑制 ,中毒后 2hAChE仍无明显回升。 (3)缺氧复合梭曼中毒对犬全血AChE的抑制速度和抑制程度都较平原中毒组有增高的趋势。而对于大鼠组织来说 ,其AChE的抑制速度明显快于平原中毒组 ,抑制程度也偏重 ,且存在一定的剂量效应关系。(4)缺氧复合梭曼中毒对大鼠全血AChE的抑制峰提前出现 ,但抑制程度相对轻些。以上结果表明在缺氧条件下血液中AChE的活性变化与梭曼的毒性并不呈平行关系 ,而脑组织中AChE的变化一定程度上可反映梭曼的毒性程度。     

Neurotoxic effects of low-level chronic acephate exposure in rats

Rats were administered the organophosphorus insecticide acephate at 1.0 or 10.0 mg/kg.day for 15 weeks. Blood and brain samples were collected at the end of the treatment and analyzed for cholinesterase, acetylcholinesterase, and glutamic acid decarboxylase activities and catecholamine and amino acid levels. No significant inhibition in the activity of brain AChE was noted at doses of 1.0 or 10.0 mg/kg.day. Low levels of acephate exposure (1.0 mg/kg.day), which did not alter plasma cholinesterase or RBC acetylcholinesterase activity levels, resulted in a significant elevation of plasma epinephrine and norepinephrine levels. Decreased GABA, dopamine, and tyrosine levels and glutamic acid decarboxylase activity were observed in brains of these rats. Similar changes occurred in rats exposed to 10 mg of acephate/kg.day; however, plasma cholinesterase and RBC acetylcholinesterase activities were inhibited. These observations suggest that chronic exposure to acephate altered the activity of the noncholinergic system without altering the cholinergic activity, and that low-level chronic exposure to organophosphorous compounds cannot be predicted by measuring the ChE or AChE enzyme activities.     

Repeated malathion exposure induces behavioral impairment and AChE activity inhibition in brains of rat pups

The present study evaluated if repeated malathion administration would cause behavioral impairment in rat pups. Na⁺ K⁺ ATPase and acetylcholinesterase (AChE) activities were investigated in brains of rat pups. Malathion was administered (100 or 200 mg/kg) orally (p.o.), once a day for four consecutive days. Rat pups were submitted to behavioral tests on the 5th day, 24 h after the last malathion administration. Malathion at the dose of 200 mg/kg caused a significant increase in the negative geotaxis latency and a decrease in the rotarod latency of rat pups. Rat pups exposed to malathion at both doses showed a significant decrease in the forelimb support latency and an inhibition of brain AChE activity. Repeated exposure of rat pups to malathion caused a decrease in motor coordination, vestibular function and muscular strength/coordination. The brain activity of AChE is involved in the behavioral alterations caused by malathion in rat pups.     

Evaluation of toxic effects of the organophosphorus insecticide azinphos-methyl in experimentally and naturally exposed birds

Laboratory and field studies were conducted to evaluate the effects of the organophosphorus insecticide, azinphosmethyl, on bird populations and into the possibility of assessing toxic hazard by a non-destructive biomarker such as BChE inhibition. Japanese quail were treated with increasing doses of azinphos-methyl (0.5, 5, and 50 mg/kg) and sacrificed 7 and 24 h later. Serum BChE and CbE, brain AChE, and liver microsomal CbE activities showed different patterns of inhibition. The maximum inhibition of BChE and CbE usually occurred 7 h after treatment, whereas the effect on AChE was greater at 24 h. A positive correlation was found between BChE and AChE, 7 and 24 h after treatment. This correlation could serve as the foundation for a theoretical model for assessing toxic hazard through non-destructive biomarkers. The only effect on brain AChE was detected in the group treated with the highest concentrations of azinphos-methyl (50 mg/kg). Fugacity model calculations showed that such massive concentrations are very unlikely to occur under natural conditions after agricultural use of the compound.The non-destructive biomarker was used to test a population of tree sparrows living in a cherry orchard sprayed once with azinphos-methyl. No inhibition of BChE activity was found 24 h after application, and it was therefore concluded that the concentration of the insecticide used did not constitute a hazard for the birds.     

维生素E补充对外周血细胞活性的影响及机制研究

目的观察不同剂量维生素E(VE)补充对大鼠外周血淋巴细胞增殖活性和抗DNA氧化损伤能力以及红细胞膜流动性的影响。方法将48只Wistar大鼠随机分为对照组和VE1、VE2及VE3三个VE补充组,各组VE摄入量分别为每天7.5、50、200和750IUkgbw,实验期为8周。实验结束后无痛处死动物并留取全血,分别测定血浆VE和MDA含量,分析红细胞膜GSHPx活性、红细胞膜流动性、淋巴细胞转化率及DNA氧化损伤。结果3个干预组血浆VE水平较对照组明显升高(P<0.05);50IUkgbw·dVE(VE1)组血浆MDA含量为(2.29±0.55)nmolml,显著低于其它三组(P<0.05),红细胞膜GSHPx活性为(367.17±129.86)Umgprot,明显高于其它三组(P<0.05);与对照、VE2、VE3组相比,VE1组淋巴细胞转化率分别提高了261.86%、199.23%、412.97%(P<0.05),10μmolLH2O2诱导的DNA氧化损伤程度显著降低(P<0.05);VE1组红细胞膜P、η值明显低于其它三组(P<0.05),即该组膜流动性显著提高。结论本实验揭示VE能明显改善红细胞膜流动性、提高淋巴细胞DNA抗氧化能力及增殖活性的有效补充剂量为50IUkgbw·d;补充剂量过大时未观察到类似作用,甚至显示细胞功能下降。     

Assessment of the delayed neurotoxicity of tributyl phosphate, tributoxyethyl phosphate, and dibutylphenyl phosphate

There industrial organophosphorus compounds were tested for their ability to cause organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the adult hen. The compounds tested were tributyl phosphate (TBP), tributoxyethyl phosphate (TBEP), and dibutylphenyl phosphate (DBPP). The acute oral LD50 of TBP and DBPP were estimated to be 1,863 and 1,500 mg/kg, respectively, and the dose equal to the LD50 was used as a test dose. The acute oral LD50 of TBEP was greater than 5,000 mg/kg and 5,000 mg/kg was used as a test dose. An oral dose of 750 mg tri-o-cresyl phosphate (TOCP) was used as a positive control. For the acute delayed neurotoxicity test, hens were given two test doses of the test materials 21 days apart and killed 21 days after the second dose. None of the hens given TBP, TBEP, or DBPP exhibited nerve damage or clinical signs which distinguished them from untreated control animals. A single dose of TOCP resulted in paralysis and a histopathological profile typical of a distal neuropathy. For the assay of the inhibition of esterases, hens were killed 24 hours after a single dose equal to the greater of either the LD50 or 5000 mg/kg. TOCP administration resulted in over 90% inhibition of brain neurotoxic esterase (NTE), but none of the other three compounds inhibited NTE to an extent (greater than 70%) which would be expected to result in OPIDN. Administration of TOCP, TBEP, or DBPP resulted in approximately a 70% decrease in plasma butyrylcholinesterase (BuChE) activity. TBP caused a 2-3 fold increase in BuChE activity. TBEP administration resulted in about 45% inhibition of acetycholinesterase (AChE) in brain. These results indicate that TBP, TBEP, and DBPP are all unlikely to cause OPIDN with any single sublethal dose.     

孕期和哺乳期母鼠饮水砷暴露对子代大鼠脑组织神经递质代谢酶的影响

目的了解砷对神经递质代谢酶的影响,探讨砷对学习、记忆能力影响的机制。方法选取清洁级Wistar大鼠,按雌∶雄为2∶1合笼。将64只孕鼠随机分为3个暴露组（分别为10、50、100mg/L剂量组）和1个对照组（蒸馏水）。暴露组于妊娠第6天（胎鼠器官分化开始）开始用NaAsO2溶液进行饮水染毒。仔鼠出生后,母鼠继续染毒。仔鼠出生后28d断乳,染毒至出生后第42天。在仔鼠出生后第0、28、42天,测量其大脑皮质和海马中谷氨酰胺合酶（GS）、乙酰胆碱酯酶（AChE）活力。结果出生后第0、28、42天,各暴露组子鼠脑皮质和海马中GS活力与对照组比较,经方差分析,差异均无统计学意义（P〉0.05）。出生后第0天,各组仔鼠的脑组织中AChE活力比较,经方差分析,差异无统计学意义（P〉0.05）。出生后第28、42天,100mg/L组子鼠脑海马中AChE活力高于对照组,差异均有统计学意义（P〈0.05）;且AChE活力均随染毒剂量的增加而增强,相关系数分别为0.408和0.374,呈统计学正相关（P〈0.05）,有明显的剂量-效应关系;其他各组仔鼠脑皮质AChE活力比较,经方差分析,差异均无统计学意义（P〉0.05）。结论砷暴露能够引起发育中的仔鼠脑组织AChE活力改变,可能会导致相应的中枢神经系统的一些改变。