抗凝血灭鼠剂大隆和鼠得克的生物学效果评价

大隆(brodifacoum)和鼠得克(difenacoum)是1975-1976年新发展的第二代抗凝血灭鼠剂,化学名称分别为3-(3-(对溴联苯基)-1,2,3,4-四氢化萘基)-4-羟基香豆素和3-(3-联苯基-1,2,3,4-四氢化萘基)-4羟基香豆素。这一类抗凝血灭鼠剂有2个突出的特性:(1)能杀灭抗药性鼠种,指对杀鼠灵(warfarin)产生抗药的鼠种,(2)兼有急性和慢性灭鼠剂的优点,单剂量对多种鼠类都有防制效果。这样不仅可以解决鼠类对杀鼠灵的抗药问题,而且可以节约灭鼠用粮和人力,有可能使抗凝血灭鼠剂推广用于防制野鼠。根据全国除四害规划安排,军事医学科学院微生物流行病研究所于1979年合成了这2种灭鼠剂样品,供全国新药协作组15个单位进行生物学效果评价。本文为部份试验结果。     

鼠类对抗凝血类灭鼠剂抗药性的遗传机制

抗凝血类灭鼠剂是鼠类化学防治过程中最常用的,然而鼠类对抗凝血类灭鼠剂的抗药性极大地降低了灭鼠的效率.鼠类可以通过多种分子途径产生抗药性,维生素K环氧化物还原酶复合体,亚单位1基因是抗凝血类灭鼠剂的靶基因,该基因上的氨基酸变异是鼠类产生抗性的主要途径,此外,细胞色素氧化酶P450基因、Calumin基因等也参与介导鼠类的抗药性.本文简单总结了全世界鼠类抗药性的现状,重点介绍了鼠类产生抗药性的分子机制及最新研究进展.     

青藏高原5种害鼠D型肉毒素抗性相关基因VAMP1的序列分析

突触小泡相关膜蛋白1基因(VAMP1)的变异是导致鼠类对D型肉毒梭毒素灭鼠剂产生抗性的主要原因。本研究利用转录组测序的方法,分析青藏高原地区5种主要害鼠:高原鼠兔(Ochotona curzoniae)、高原鼢鼠(Eospalax baileyi)、长尾仓鼠(Cricetulus longicaudatus)、青海松田鼠(Neodon fuscus)和喜马拉雅旱獭(Marmota himalayana)的VAMP1序列信息。同时,分别采集来自5个地理种群的58只高原鼠兔和59只高原鼢鼠,对VAMP1基因第二外显子区序列进行分析。结果显示,从转录组组装文件中成功获得5种动物的VAMP1基因全序列,长度均为357 bp,共检测到46个核苷酸变异位点和4个氨基酸变异位点,但未发现与D型肉毒素抗性相关的氨基酸位点。对高原鼠兔群体和高原鼢鼠群体的VAMP1基因第二外显子序列的分析显示,高原鼠兔所有个体的序列高度保守,而在高原鼢鼠中则存在一个同义突变位点,但两物种在D型肉毒素抗性相关位点上都未监测出位点变异。该研究结果提示,D型肉毒杀鼠剂在青藏高原地区害鼠防治方面应该可以长期发挥重要作用。     

0．025％杀鼠灵灭鼠效果观察

杀鼠灵是我国第二代抗凝血灭鼠剂。为了解其效果和使用方法,我们于1987年2-3月在湖北某宾馆进行了室内外灭鼠效果观察,结果报告如下。 试验药物 杀鼠灵原药系张家口市鼠药厂1983年产品,批号2-33,纯度为99.45％。     

“大隆”间隔与连续投药法毒杀家鼠灭效比较

大隆(Brodifacoum)系第二代抗凝血杀鼠剂,它能杀死对抗凝血杀鼠剂有抗性的“超级鼠”,单次投毒有效。为了取得应用经验,我们选择以黄胸鼠(Rattus flavipectus Milne—Edwards)为优势种,褐家鼠(Rattus norvegicus Berkenhout)为常见种的家鼠现场,作了间隔与连续投药法灭效比较,综述如下: 方法     

新杀鼠剂“鼠大克”对高原鼠兔(Ochotona curzoniae)的毒效试验

Difenacoum是近年来新出现的抗凝血杀鼠剂新品种。在国外,它的粒状毒饵Ratak已出现于商品市场(以下本文统一采用“鼠大克”作为Difenacoum及Ratak的中文名称)。 鼠大克是为了对付50年代以来,由于广泛应用华法令(warfarin)等一系列抗凝血杀鼠剂以后产生的褐家鼠和小家鼠等抗性鼠种群,而投入使用的新一代抗凝血杀鼠剂品种之一。鼠大克在英国做为商品杀鼠剂已出售几年了,使用它防治抗药性黑家鼠(Rat     

大隆灭鼠试验

大隆(TALON,brodifacoum)是一种香豆素类有机化合物。是70年代后期国外出现的第二代抗凝血灭鼠剂。大隆灭鼠剂与第一代抗凝血灭鼠剂比较有下述优点: 1.使用浓度低。采用单剂量投药就可有效     

杀鼠灵灭鼠试验

杀鼠灵(Warfarin)是香豆素类抗凝血灭鼠剂,我们于1984年3—5月对2.5/万的杀鼠灵毒饵的灭鼠效果作了初步试验观察,结果如下。 (一)小现场灭鼠效果 为开展大面积灭鼠工作积累经验,在本所实验动物房(约200平方米)作灭鼠效果观察,投药前用食饵消耗法测定鼠密度,然后投放毒饵65堆,每堆20克,每天补充消耗的毒饵,连续投放8天,过10天后再用食饵消耗法测定鼠密度,结果灭鼠率达87.5％,投放毒饵第3天拣到死鼠1只,第4天9只,第5天6只,第6天5     

黄胸鼠对抗凝血剂抗药性初步调查

鼠类对抗凝血剂的抗药性有变义现象,对香豆素类有抗药性,对茚二酮类也有抗药性。为了解多年来使用抗凝血杀鼠剂防治黄胸鼠(Rattus flavipetus),我们于1980年在福建省云霄县进行了一次试验性调查。     

鼠得克Difenacoum对黑线姬鼠、高山姬鼠的毒力测定及适口性试验

鼠得克Difenacoum是第二代抗凝血杀鼠剂,其化学名称为3-(3-P二二苯基—1、2、3、4—四羟基萘基—4—羟基香豆素)。本药剂对有耐药性的鼠类效果更为显著。为确定其对黑线姬鼠、高山姬鼠的毒力(按抗凝血灭鼠剂常规测定法作一或三次灌胃测定)、适口性等毒杀效果,特作下述实验,现将实验情况简报于后:一、毒力测定:(一)药物:系军事医学科学院流行病学研究所1979年合成的纯品一克。(二)动物:野外捕获的黑线姬鼠、高山姬鼠在实验室饲养7～20天,分别选择20～35克健康成年鼠8—10只,雌雄各半备用。(三)给药:将鼠得克按所需浓度,精密称取后,用聚乙二…     

湖南农业鼠害防治技术研究 Ⅰ.害鼠的种类、害区和与防治有关的生物学特性

本文报道湖南省的农业鼠害防治技术,内容包括农业鼠害、鼠种组成、鼠害类型、鼠类生态等生物学特性,为大面积全生境灭鼠提供综合性的防治技术措施。     

The geographic distribution and host range of Capillaria hepatica (Bancroft) (Nematoda) in Australia.

The geographic distribution, host range and prevalence of Capillaria hepatica were recorded in 4629 house mice, Mus domesticus, 263 black rats, Rattus rattus, and 58 Norway rats, R. norvegicus. The parasite was found at five localities, all in or near large towns along the coast. The two Rattus species appeared to be the primary hosts of C. hepatica in Australia. Published and unpublished data on helminth infections of Australian native mammals from 1162 murids (26 species), 3018 marsupials (67 species) and 99 monotremes (two species) were compiled. Only seven animals from three murid species were infected with C. hepatica; all were from the same rainforest in northern Queensland. C. hepatica was distributed widely, occurring in the house mouse, black rat and Norway rat on a 10,850 ha farm but there was no infection in cattle, sheep or goats (abattoir records). Also, 52 rabbits, four cats and one fox (shot samples) and 27 marsupial mice, Sminthopsis crassicaudata (museum specimens), had no sign of C. hepatica infection. Overall, the results indicate that transmission of C. hepatica to native, domestic and feral mammals is rare, presumably because of ecological constraints on egg embryonation and survival. In the light of these findings, the potential use of C. hepatica as a biological agent to control mouse plagues in Australia is discussed.     

斑鳢肝脏解偶联蛋白2cDNA核心片断的克隆及分析

解偶联蛋白2(uncouplingprotein 2,UCP2)可使氧化磷酸化解偶联。本研究首次成功从斑鳢(Channa maculata)肝脏通过简并引物克隆获得UCP2基因cDNA核心序列,该片段长502bp,编码167个氨基酸残基。使用vector NTI suite 6.0软件进行氨基酸同源性序列比较分析表明,斑鳢UCP2与真鲷、鲤鱼、草鱼、斑马鱼UCP2同源性高达91%、73%、72%、71%,与人、大鼠、小鼠UCP2同源性较高为70%、71%、70%。UCP2编码区在鱼类、哺乳类中均具有较高保守性,提示着脊椎动物UCP2可能在线粒体有氧呼吸代谢过程中承担某种最基本的生命功能。     

北京地区鼠类群落结构的研究

在生态系统中,啮齿动物为食物链的主要环节之一,研究鼠类群落结构及作用是评价北京地区环境生态的重要内容。有关鼠类群落的研究,国外已有较多报道(Hafner,1977;Grant和Birney,1979),近年来也引起我国动物生态学工作者的注意(刘季科,1979;钟文勤,1981;周庆强,1982)。而北京地区尚无这方面的报道。 根据我们1982年8月到1983年底在北京地区的调查,兽类区系中啮齿类约占34%,其中约一半种类为不同环境中的主要种类,现将鼠类群落结构的研究报道如下。     

Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea)

and 1988. Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea). International Journal for Parasitology 18: 1087–1092. Cercopithifilaria johnstoni (Nematoda:Filarioidea) occurs in the subcutaneous connective tissues of a spectrum of native murid and marsupial hosts in Eastern Australia. Life cycle studies revealed that: (i) microfilaria occur in lymphatic capillaries and extravascular connective tissue of the dermis (= ‘skin-inhabiting’), (ii) ixodid ticks, particularly Ixodes trichosuri, are intermediate hosts in nature, (iii) development from microfilariae to infective third-stage larva occurs only while the tick is off the host, that is, during ecdysis from larva to nymph or from nymph to adult. Transmission of C. johnstoni in a wild population of bush rats (Rattus fuscipes) occurred in summer and winter, and was associated with peaks in the number of larval and/or nymphal stages of ticks on rats. C. johnstoni was transmitted experimentally to bandicoots (Isoodon macrourus, Perameles nasuta), bush rats and laboratory rats (R. norvegicus), indirectly by subcutaneous inoculation of third-stage larvae and directly by tick feeding. The prepatent period was approximately 3 months and the longest duration of microfilariae in the ‘ skin’ was more than 25 months. Dermal and ocular lesions were observed in R. fuscipes. The host-parasite relationship has the potential for development as an inexpensive and practical model for human onchocerciasis.     

Relation between Intensity of Biocide Practice and Residues of Anticoagulant Rodenticides in Red Foxes (Vulpes vulpes)

Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations for biocidal and plant protection purposes. This can lead to AR exposure of non-target small mammals and their predators, which is known from several regions of the world. However, drivers of exposure variation are usually not known. To identify environmental drivers of AR exposure in non-targets we analyzed 331 liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used local parameters (percentage of urban area and livestock density) to test for associations to residue occurrence. 59.8% of samples collected across Germany contained at least one rodenticide, in 20.2% of cases at levels at which biological effects are suspected. Second generation anticoagulants (mainly brodifacoum and bromadiolone) occurred more often than first generation anticoagulants. Local livestock density and the percentage of urban area were good indicators for AR residue occurrence. There was a positive association between pooled ARs and brodifacoum occurrence with livestock density as well as of pooled ARs, brodifacoum and difenacoum occurrence with the percentage of urban area on administrative district level. Pig holding drove associations of livestock density to AR residue occurrence in foxes. Therefore, risk mitigation strategies should focus on areas of high pig density and on highly urbanized areas to minimize non-target risk.     

Spatial and temporal patterns of brown rat (Rattus norvegicus) abundance variation in poultry farms

The temporal and spatial patterns of rat abundance variations were studied, and which factors might affect these patterns in poultry farms. Forty-eight poultry farms were sampled from spring 1999 to winter 2001 in Buenos Aires, Argentina. Environmental variables of farms, meteorological variables and distances among farms were registered to evaluate a possible association with rat abundance estimated by trap success. Rattus norvegicus was the dominant rat species in the study area. Rat abundance did not vary temporally and there was reproduction at all times. Trap success was more similar among neighboured farms than among farms further apart. Contrary to the abundance of other small rodents, rat abundance was not significantly related to farm characteristics. The lack of coincidence between rats and other small rodents suggests the existence of a differential response of rats to environmental factors of the poultry farms.     

Normal and warfarin-resistant rat hepatocyte metabolism of vitamin K 2,3-epoxide: evidence for multiple pathways of hydroxyvitamin K formation

Vitamin K and 3- (and/or 2)-hydroxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone (hydroxyvitamin K) have been identified as metabolites of vitamin K 2,3-epoxide incubated with hepatocytes isolated from normal and warfarin-resistant rats. Dithiothreitol added to the extracellular medium differentially enhanced the formation of both metabolites: hydroxyvitamin K formation, almost undetectable in the absence of dithiothreitol, was particularly affected. Addition of the vitamin K 2,3-epoxide reductase inhibitors warfarin (5 to 100 microM) and brodifacoum (1 to 5 microM) to normal rat hepatocyte cultures produced a slight increase in hydroxyvitamin K formation and a marked inhibition of vitamin K formation. Brodifacoum was a weak inhibitor of hydroxyvitamin K formation at higher concentrations. Hepatocytes from warfarin-resistant rats catalyzed hydroxyvitamin K formation 1.5 to 2 times faster and vitamin K formation 1.5 to 2 times slower than did normal rat hepatocytes. The addition of warfarin to these cultures had no effect on epoxide metabolism to hydroxyvitamin K and only partially diminished metabolism to vitamin K. In contrast, brodifacoum (1 microM) addition produced 50% inhibition of hydroxyvitamin K formation and almost complete inhibition of vitamin K formation. These data suggest that in resistant, but not in normal rat hepatocytes, the vitamin K 2,3-epoxide reductase makes a significant contribution to hydroxyvitamin K formation. A second sulfhydryl-dependent pathway, present in both strains, is also involved in the formation of this metabolite. They also suggest that in resistant rats, warfarin inhibition of the vitamin K 2,3-epoxide reductase, and presumably the sulfhydryl-dependent vitamin K reductase, is incomplete and independent of concentration.     

Residues of brodifacoum and other anticoagulant pesticides in target and non‐target species,Nelson Lakes National Park,New Zealand

Abstract

Cereal‐based bait containing 20 ppm brodifacoum was used in bait stations continuously from December 1997 to August 2000 in the Rotoiti Nature Recovery Project area, for controlling brushtail possum (Trichosurus vulpecula), ship rat (Rattus rattus), and house mouse (Mus musculus) populations. Concurrently (and before and after), baits containing brodifacoum, bromadiolone, flocoumafen, coumatetralyl, or warfarin were also used in St Arnaud village and on farms immediately adjacent to the project area. Brodifacoum residues were detected in the livers of 234 mammals from eight species, and two birds from two species captured alive, and a further seven birds from five species found dead in the project area (cause of death unknown). The highest concentration of brodifacoum residues in mammalian livers was recorded during the period brodifacoum was used in the project area. However, residues were present in the livers of some individuals at least 24 months after brodifacoum use in the project area stopped. These residues may have persisted in animals surviving brodifacoum use in the project area, and/or been transported into the area by animals moving to and from the adjacent village and farms, where brodifacoum use continued. Residues of flocoumafen, coumatetralyl, or warfarin, used only in the village and on farms, were also detected in the livers of animals captured up to at least 8 km from the nearest source. The results concur with other studies cautioning against indiscriminate or prolonged use of persistent anticoagulants for vertebrate pest control. However, the risks from such pesticides must be balanced against the demonstrable benefits of reducing pest abundance.     

抗阻训练对增龄大鼠骨骼肌线粒体功能的影响*

目的: 从线粒体动力学的角度,探讨抗阻运动对增龄大鼠骨骼肌线粒体功能的影响。方法: 40只雄性SD大鼠随机分为4组:2月龄安静对照组(C1组)、2月龄抗阻运动训练组(R1组)、6月龄安静对照组(C2组)、6月龄抗阻运动训练组(R2组),每组10只。C1、C2组正常喂养,R1、R2组大鼠进行跑台坡度为35°,速度为15 m/min的抗阻运动,一次跑动15 s,间歇30 s,4次为一组,组间间歇3 min,3组为一次循环,一天为2个循环,循环间歇10 min,每周6 d,共8周。采用Western blot法测定各组大鼠股四头肌线粒体融合蛋白2(Mfn2)、GTP酶1(DRP1) 蛋白含量,使用流式细胞仪测定各组大鼠股四头肌线粒体膜电位(ΔΨm)、活性氧(ROS)和游离钙(Ca²⁺)水平。结果: ① 与C1组相比,R1组大鼠DRP1蛋白升高(P＜0.01)、Mfn2蛋白无显著变化,C2组大鼠DRP1、Mfn2蛋白均降低(P均＜0.01);与C2组相比,R2组大鼠DRP1、Mfn2蛋白均升高(P＜0.01,P＜0.05);与R1组相比,R2组DRP1、Mfn2蛋白均降低(P＜0.01,P＜0.05)。② 与C1组相比,R1组Ca²⁺含量降低(P＜0.01)、C2组Ca²⁺含量升高(P＜0.01);与C2组相比,R2组Ca²⁺含量降低(P＜0.01);与R1组相比,R2组Ca²⁺含量升高(P＜0.01)。③ 与C1组相比,R1组ROS含量有所上升,但无显著性差异,C2组ROS含量升高(P＜0.01);与C2组相比,R2组ROS含量降低(P＜0.01);与R1组相比,R2组ROS含量升高(P＜0.01)。④ 与C1组相比,C2组ΔΨm降低(P＜0.01);与C2组相比,R2组ΔΨm升高(P＜0.01);与R1组相比,R2组ΔΨm有所降低,但无统计学差异。结论: 大鼠增龄过程中股四头肌线粒体出现Ca²⁺堆积、活性氧增多、线粒体膜电位下降、融合蛋白减少等现象,抗阻训练可有效改善这些变化。