研究论文

澳门地区褐家鼠对溴鼠灵的抗性检测及其Vkorc1基因多态性分析

  • 郭敏 ,
  • 梁捷 ,
  • 何向阳 ,
  • 欧伟新 ,
  • 彭定雄 ,
  • 麦展昭 ,
  • 黄海涛 ,
  • 张礼标
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  • 1.广东省科学院动物研究所,广东省动物保护与资源利用重点实验室,广东省野生动物保护与利用公共实验室,广州 510260
    2.澳门市政署,澳门特别行政区 999078
    3.广东科建生物技术有限公司,广州 510260
郭敏 (1983- ),男,主要从事动物生态及行为机制研究.E-mail: guomin5208@163.com
zhanglb@giz.gd.cn
Corresponding authors, E-mail: kejian@giz.gd.cn

收稿日期: 2021-06-22

  录用日期: 2022-03-10

  网络出版日期: 2022-12-02

基金资助

广东省科学院建设国内一流研究机构行动专项资金项目(2021GDASYL-20210103052);广东省科技计划项目(2021B1212110003)

An investigation of brodifacoum resistance and Vkorc1 gene polymorphism in the Rattus norvegicus from Macao

  • Min GUO ,
  • Jie LIANG ,
  • Xiangyang HE ,
  • Weixin OU ,
  • Dingxiong PENG ,
  • Zhanzhao MAI ,
  • Haitao HUANG ,
  • Libiao ZHANG
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  • 1.Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China
    2.The Municipal Affairs Bureau, Macao 999078, China
    3.Guangdong Kejian Biotechnology Co. , Ltd, Guangzhou 510260, China

Received date: 2021-06-22

  Accepted date: 2022-03-10

  Online published: 2022-12-02

摘要

第二代抗凝血灭鼠剂因比第一代抗凝血灭鼠剂有更好的灭杀效果和安全性而被广泛使用,但长期使用同样也存在引发鼠类抗性的隐患。近年,学者已发现了第二代抗凝血灭鼠剂溴敌隆 (bromadiolone) 和鼠得克 (difenacoum) 的抗性鼠。溴鼠灵 (brodifacoum) 是一种目前在国内广泛使用且毒性极强的第二代抗凝血灭鼠剂,能引发鼠类凝血功能障碍和细胞毒性,但对于溴鼠灵是否已驱动鼠类发生抗性进化尚不清楚。澳门地区从1995年开始持续使用溴鼠灵,为研究鼠类对溴鼠灵的抗药性进化提供了良好模型。本研究于2019年10—12月在澳门地区共捕获61只褐家鼠,对其中44只开展了LFP实验 (0.005%溴鼠灵),实验鼠的平均摄毒量为 (15.28 ± 1.40) mg/kg,在7天内全部死亡。此外,对全部61只褐家鼠的维生素K环氧化物还原酶复合体亚单位1 (vitamin K-epoxide reductas complex 1, Vkorc1) 的基因序列测定表明,在Vkorc1基因外显子的已知抗药关联位点处未检测到非同义核苷酸突变,但检测到2个同义核苷酸突变 [第68位氨基酸:H (CAC)-H (CAT),突变发生率为100%;第82位氨基酸:I (ATA)-I (ATT),突变发生率为32.72%]。该研究表明,使用溴鼠灵25年后,澳门地区褐家鼠虽没有产生群体抗药性,但仍需持续监测抗药性的发生和发展。

本文引用格式

郭敏 , 梁捷 , 何向阳 , 欧伟新 , 彭定雄 , 麦展昭 , 黄海涛 , 张礼标 . 澳门地区褐家鼠对溴鼠灵的抗性检测及其Vkorc1基因多态性分析[J]. 兽类学报, 2022 , 42(6) : 698 -704 . DOI: 10.16829/j.slxb.150579

Abstract

The 2nd-generation anticoagulant rodenticides (ARs) are widely used for their higher eradicative rate and safety than the 1st-generation ARs. However, long-term use of the 2nd generation ARs could cause AR resistance in rats. Recently, researchers have reported resistance to the 2nd generation ARs bromadiolone and difenacoum in rats. Brodifacoum is a widely used 2nd-generation ARs of high toxicity that causes coagulation dysfunction and cytotoxicity in rats, but at present, the evolution of rat resistance against brodifacoum remains unclear. Macao has continuously used brodifacoum since 1995, allowing us to explore the development of rat resistance against brodifacoum. In this study, a total of 61 rats (Rattus norvegicus) were captured in Macao from October to December 2019. Among them, 44 rats were chosen to perform the LFP test (with 0.005% brodifacoum). The results showed that these rats consumed (15.28 ± 1.40) mg/kg (mean ± SE) brodifacoum on average, resulting in all of them dying within 7 days. Furthermore, we detected the nucleotide polymorphism of vitamin K-epoxide reductase complex 1 (Vkorc1) in all the 61 captured rats, and found none of the previously identified AR-resistant nonsynonymous mutations in Vkorc1 genes, but did detect 2 synonymous mutations [at amino acid locus 68: H (CAC)-H (CAT), mutation rate: 100%; and amino acid locus 82: I (ATA)-I (ATT), mutation rate: 32.72%]. The fact that none of the rats were brodifacoum-resistant suggests that no resistance propagated in R. norvegicus population after 25 years of use of brodifacoum in Macao. Nevertheless, persistent surveillance on the development of rat resistance to brodifacoum in the region is still needed.

参考文献

null Alomar H, Chabert A, Coeurdassier M, Vey D, Berny P. 2018. Accumulation of anticoagulant rodenticides (chlorophacinone, bromadiolone and brodifacoum) in a non?target invertebrate, the slug, Deroceras reticulatum . Science of the Total Environment, 610-611: 576-582.
null Ayala I, Rodriguez M J, Martos N, Zilberschtein J, Ruiz I, Motas M. 2007. Fatal brodifacoum poisoning in a pony. Canadian Veterinary Journal-Revue Veterinaire Canadienne, 48 (6): 627-629.
null Bachmann K A, Sullivan T J. 1983. Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin?sensitive rats. Pharmacology, 27 (5): 281-288.
null Baker J T, Graversen C H, Files J E. 2002. Brodifacoum toxicity. Journal of the Mississippi State Medical Association, 43 (4): 106-107.
null Boermans H J, Johnstone I, Black W D, Murphy M. 1991. Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse. Canadian Journal of Veterinary Research-Revue Canadienne de Recherche Veterinaire, 55 (1): 21-27.
null Booth K. 1989. Brodifacoum poisoning in a dog. New Zealand Veterinary Journal, 37 (2): 74-75.
null Booth G S, Mody P Z. 2016. Brodifacoum inhalation and its clinical manifestations in a 21?year?old caucasian man. Laboratory Medicine, 47 (1): 63-66.
null Breckenridge A M, Cholerton S, Hart J A, Park B K, Scott A K. 1985. A study of the relationship between the pharmacokinetics and the pharmacodynamics of the 4-hydroxycoumarin anticoagulants warfarin, difenacoum and brodifacoum in the rabbit. British Journal of Pharmacology, 84 (1): 81-91.
null Buckle A P, Klemann N, Prescott C V. 2012. Brodifacoum is effective against Norway rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance in Westphalia, Germany. Pest Management Science, 68 (12): 1579-1585.
null Chen W E, Li X Y, Zhong L Q, Lin Y, Yu Q Y. 2016. The palatability and field deratization effect of 0.005% brodifacoum baits. Chinese Journal of Hygienic Insecticides & Equipments, 22 (3): 239-241. (in Chinese)
null Chen W S, Wang T Z, Yang B C, Gu W Z, Yang L, Ye L X. 2007. Analysis on the efficacy of killing rats with brodifacoum poison bait in field. Chinese Journal of Hygienic Insecticides & Equipments, 13 (3): 179-181. (in Chinese)
null Chu M J, Wang L, Li X X, Huang L L, Wang X H, Sang L L, Zhang S J, Tao C Y, Chen Y, Wang Z Q. 2018. Sequence analysis of the promoter and the second exon of vitamin K epoxide reductase complex subunit 1 VKORC1 in commensal rodents. Chinese Journal of Hygienic Insecticides & Equipments, 24 (6): 568-571. (in Chinese)
null Eason C T, Murphy E C, Wright G R, Spurr E B. 2002. Assessment of risks of brodifacoum to non?target birds and mammals in New Zealand. Ecotoxicology, 11 (1): 35-48.
null Endepols S, Klemann N, Song Y, Kohn M H. 2013. Vkorc1 variation in house mice during warfarin and difenacoum field trials. Pest Management Science, 69 (3): 409-413.
null Fitzgerald S D, Martinez J, Buchweitz J P. 2018. An apparent case of brodifacoum toxicosis in a whelping dog. Journal of Veterinary Diagnostic Investigation, 30 (1): 169-171.
null Geduhn A, Esther A, Schenke D, Mattes H, Jacob J. 2014. Spatial and temporal exposure patterns in non?target small mammals during brodifacoum rat control. Science of the Total Environment, 496: 328-338.
null Goulois J, Chapuzet A, Lambert V, Chatron N, Tchertanov L, Legros L, Benoit E, Lattard V. 2016. Evidence of a target resistance to antivitamin K rodenticides in the roof rat Rattus rattus: identification and characterisation of a novel Y25F mutation in the Vkorc1 gene. Pest Management Science, 72 (3): 544-550.
null Gul N, Yigit N, Saygili F, Demirel E, Genis C. 2016. Comparison of the effects of difenacoum and brodifacoum on the ultrastructure of rat liver cells. Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology, 67 (3): 204-209.
null Kalinin S, Marangoni N, Kowal K, Dey A, Lis K, Brodsky S, van Breemen R, Hauck Z, Ripper R, Rubinstein I, Weinberg G, Feinstein D L. 2017. The long?lasting rodenticide brodifacoum induces neuropathology in adult male rats. Toxicological Sciences, 159 (1): 224-237.
null Liu G, Zeng H. 2002. An introduction to rodenticide. Chinese Journal of Chemical Education, 23 (6): 1-2, 28. (in Chinese)
null Mooney J, Lynch M R, Prescott C V, Clegg T, Loughlin M, Hannon B, Moore C, Faulkner R. 2018. VKORC1 sequence variants associated with resistance to anticoagulant rodenticides in irish populations of Rattus norvegicus and Mus musculus domesticus. Scientific Reports, 8 (1): 4535.
null Rost S, Pelz H J, Menzel S, MacNicoll A D, Leon V, Song K J, Jakel T, Oldenburg J, Muller C R. 2009. Novel mutations in the VKORC1 gene of wild rats and mice-a response to 50 years of selection pressure by warfarin? BMC Genetics, 10: 4.
null Song M L, Yang J, Qu J L, Wang H L. 2002. Evaluation on the palatability and killing efficacy of brodifacoum wax-mass against mouse. Chinese Journal of Hygienic Insecticides & Equipments, 8 (3): 29-31. (in Chinese)
null Walther B, Geduhn A, Schenke D, Jacob J. 2021. Exposure of passerine birds to brodifacoum during management of Norway rats on farms. Science of the Total Environment, 762: 144160.
null Wang Z Q, Li H B, Zhang S J, Chen Y, Chen D L, Liu D P, Chen S Y, Yang W C, Gu F. 2014. The link between VKORC1 gene and the anticoagulant resistance in commensal rodents in Nantong City. Chinese Journal of Hygienic Insecticides & Equipments, 20 (1): 23-25, 28. (in Chinese)
null Ware K M, Feinstein D L, Rubinstein I, Weinberg G, Rovin B H, Hebert L, Muni N, Cianciolo R E, Satoskar A A, Nadasdy T, Brodsky S V. 2015. Brodifacoum induces early hemoglobinuria and late hematuria in rats: novel rapid biomarkers of poisoning. American Journal of Nephrology, 41 (4-5): 392-399.
null Xiong M T, Tao K H, Luo Q S, Wang G H, Gong S M, Ji Y L, Dian X L, Liang W, He W P. 2003. Experimental efficiency of two anticoagulants against Rattus flavipectus and Rattus norvegicus . Journal of Medical Pest Control, 19 (5): 282-284. (in Chinese)
null Yao D D, Jiang H X, Liu F J, Feng Z Y. 2019. A study of the resistance of Rattus losea to the first?generation anticoagulant rodenticide and its correlation with the VKORC1 gene. Chinese Journal of Vector Biology and Control, 30 (6): 613-617. (in Chinese)
null 王智泉, 李海波, 章士军, 陈郁, 陈大灵, 刘大鹏, 陈宋义, 杨伟超, 顾峰. 2014. 南通市家栖鼠VKORC1基因及其抗药性的相关研究. 中华卫生杀虫药械, 20 (1): 23-25, 28.
null 石杲. 2003. 中国鼠类及其防治概述. 医学动物防制, 19 (11): 689-691.
null 刘刚, 曾虹. 2002. 灭鼠药介绍. 化学教育, 23 (6): 1-2, 28.
null 宋明亮, 杨军, 曲建立, 王洪林. 2002. 溴鼠灵蜡块对家鼠适口性和灭效的实验评价. 中华卫生杀虫药械, 8 (3): 29-31.
null 孟庆云. 2003. “人见死鼠如见虎”: 鼠疫的三次世界性大流行. 中国中医基础医学杂志, 8 (9): 42-44.
null 张涛, 吴明寿. 2007. 广东鼠形动物及其防制. 银川: 宁夏人民出版社.
null 陈心尧. 1992. 抗凝血灭鼠剂的今昔及其应用. 中国国境卫生检疫杂志, 15 (6): 377-381.
null 陈戊申, 王廷哲, 杨炳长, 古伟志, 杨磊, 叶临湘. 2007. 溴鼠灵毒饵现场杀灭家鼠效果的评价. 中华卫生杀虫药械, 13 (3): 179-181.
null 陈蔚恩, 李选云, 钟柳青, 林毅, 俞泉宇. 2016. 0.005%溴鼠灵饵剂的适口性及其现场灭鼠效果研究. 中华卫生杀虫药械, 3 (22): 239-241.
null 姚丹丹, 姜洪雪, 刘福佳, 冯志勇. 2019. 广东省江门市黄毛鼠对第一代抗凝血杀鼠剂的抗药性及其与VKORC1基因的相关性研究. 中国媒介生物学及控制杂志, 30 (6): 613-617.
null 鼠类抗药性监测协作组. 1991. 家栖鼠对抗凝血灭鼠剂抗药性的检验方法. 中国媒介生物学及控制杂志, 2 (5): 339-340.
null 褚敏捷, 王蕾, 李晓璇, 黄玲玲, 王晓慧, 桑灵丽, 章士军, 陶长余, 陈郁, 王智泉. 2018. 家栖鼠维生素K环氧化物还原酶复合物亚单位1 VKORC1基因启动子及第二外显子序列分析. 中华卫生杀虫药械, 24 (6): 58-61.
null 熊孟韬, 陶开会, 罗启松, 王光惠, 龚素明, 吉永丽, 殿学兰, 梁伟, 何伟平. 2003. 二种抗凝血灭鼠剂毒杀褐家鼠和黄胸鼠效果评价. 医学动物防制, 19 (5): 282-284.
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