Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii population...Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii populations with different basal insecticide resistance levels,and evaluated the effects of basal insecticide resistance on the resistance development and cross-resistance,as well as differences in fitness.Under the same selection pressure,Yarkant A.gossypii(with low basal insecticide resistance)evolved resistance to sulfoxaflor and acetamiprid more quickly than Jinghe A.gossypii(with high basal insecticide resistance),and the evolution of A.gossypii resistance to sulfoxaflor developed faster than acetamiprid in both Yarkant and Jinghe,Xingjiang,China.The sulfoxaflor-resistant strains selected from Yarkant and Jinghe developed significant cross-resistance to acetamiprid,imidacloprid,thiamethoxam and pymetrozine;while the acetamiprid-resistant strains developed significant cross-resistance to sulfoxaflor,imidacloprid,thiamethoxam,pymetrozine,and chlorpyrifos.The relative fitness of A.gossypii decreased as the resistance to sulfoxaflor and acetamiprid developed.The relative fitness levels of the sulfoxaflor-resistant strains(Yarkant-SulR and Jinghe-SulR)were lower than those of the acetamipridresistant strains(Yarkant-AceR and Jinghe-AceR).In addition,the relative fitness levels of sulfoxaflor-and acetamiprid-resistant strains were lower in Jinghe than in Yarkant.In summary,basal insecticide resistance of A.gossypii and insecticide type affected the evolution of resistance to insecticides in A.gossypii,as well as cross-resistance to other insecticides.The sulfoxaflor-and acetamiprid-resistant A.gossypii strains had obvious fitness costs.The results of this work will contribute to the insecticide resistance management and integrated management of A.gossypii.展开更多
Acetamiprid has a wide range of influence on physiological functions in mammals.The objective of this study was to examine the effect of acetamiprid on the reproductive function of male mice,and to study the role of o...Acetamiprid has a wide range of influence on physiological functions in mammals.The objective of this study was to examine the effect of acetamiprid on the reproductive function of male mice,and to study the role of oxidative stress in acetamiprid-induced damage to the testes.Fifty adult Kunmin male mice （25-30 g） were divided into five groups （n=10 per group）,i.e.,control,blank,acetamiprid alone,acetamiprid and vitamin E,and vitamin E alone.All groups were treated for 35 d.The results showed that acetamiprid significantly decreased the body weight and the weight of testosterone-responsive organs,such as the testis,epididymis,seminal vesicle,and prostate.Furthermore,acetamiprid also significantly reduced the serum testosterone concentration,and decreased sperm count,viability,motility,and the intactness of the acrosome （P〈0.05 for each parameter）.The mice treated with acetamiprid had damaged seminiferous tubules and Leydig cells based on the histological structure of testes;there was degeneration of the mitochondria and endoplasmic reticulum of Leydig cells.These deleterious effects of acetamiprid may be mediated by increasing oxidative stress,as acetamiprid increased malondialdehyde and nitric oxide in the testes,reduced the activity of catalase,glutathione peroxidase,superoxide dismutase,and activated p38.The concentration of acetamiprid in the testes was lower than that in liver,so did the concentrations of liver function tests,including aspartate transaminase （AST）,alanine transaminase （ALT） and alkaline phosphatase （ALP）,which suggest that male reproductive function may be affected through the indirect action of its metabolites.Vitamin E significantly ameliorated the effects of acetamiprid.We conclude that acetamiprid damages male reproductive function through inducing oxidative stress in the testes.展开更多
Objective To investigate how acetamiprid, a new insecticide, affects the activity of superoxide dismutase （SOD）, catalase （CAT）, and ATPase and the SOD isozyme patterns in two G-bacteria, E. coli K12 anti Pse.FH2,...Objective To investigate how acetamiprid, a new insecticide, affects the activity of superoxide dismutase （SOD）, catalase （CAT）, and ATPase and the SOD isozyme patterns in two G-bacteria, E. coli K12 anti Pse.FH2, and one G^＋ bactemm, B. subtilis. Methods The SOD, CAT, and ATPase specific activities of cell lysates were determined spectrophotometrically at 550 nm, 240 nm, and 660 nm, respectively, with kits A001, A016, and A007. SOD isozyme patterns were detected by native PAGE analysis. Results SOD and CAT activities in the tested bacteria increased significantly in a concentration-dependent manner after different concentrations of acetamiprid were applied. The activity of SOD in B. subtilis and Pse.FH2 was stimulated and reached the highest level after treatment with 100 mg/L acetamiprid for 0.5 h. For Pse.FH2, there was another stimulation of SOD activity after acetamiprid application for about 8.0 h and the second stimulation was stronger than the first. The stimulation by acetamiprid showed a relative lag for E. coli K12. Acetamiprid seemed to exhibit a similar effect on CAT activity of the two G bacteria and had an evident influence on ATPase activity in the three bacteria within a relatively short period. Only one SOD isozyme was detectable in Pse.FH2 and B. subtilis, while different isozyme compositions in E. coli could be detected by native PAGE analysis. Conclusion Acetamiprid causes a certain oxidative stress on the three bacteria which may not only elevate SOD and CAT activities but also generate new SOD isozymes to antagonize oxidative stress. However, this oxidative stress lasts for a relatively short time and does not cause a long-term damage.展开更多
An aerobic bacterium, capable of degrading the new chloronicotine pesticide acetamiprid, was isolated from the sludge of pesticide factory after successive enrichment cultures and named strain FH2 which is a Gram-nega...An aerobic bacterium, capable of degrading the new chloronicotine pesticide acetamiprid, was isolated from the sludge of pesticide factory after successive enrichment cultures and named strain FH2 which is a Gram-negative, rod-shaped, obligate aerobic organism with （（0.5-0.7）×（l.5-3.0））μm of cell size and with monotrichous flagellum. It was identified as a member of Pseudomonas sp. based on morphology, physio-biochemical properties, Biolog GN2, 16S rDNA sequence and phylogenetic characteristic analysis. The isolate could grow optimally at pH 7.0 and 30℃ in acetamiprid-mineral medium with 800 mg/L concentration. About 53.3% acetamiprid was degraded by strain FH2 after incubation for 14 d in acetamiprid-mineral medium and nearly 96.7% degraded when incubated in acetamiprid-yeast mineral medium at 30℃ for 14 d. This paper describes phylogenetic and degradation characterization of a pure bacterium being able to mineralize acetamiprid for the first time.展开更多
The in vitro acute cytotoxicity of the neonicotinoid insecticide acetamiprid to FG cell line, derived from the gill of flounder Paralichthys olizaceus, was tested by the three widely used endpoint bioassays-neutral r...The in vitro acute cytotoxicity of the neonicotinoid insecticide acetamiprid to FG cell line, derived from the gill of flounder Paralichthys olizaceus, was tested by the three widely used endpoint bioassays-neutral red （NR） assay, tetrazolium （MTT） assay and cell protein assay. It was found that acetamiprid was increasingly toxic to FG cells at concentrations of 1 μg/cm^3 or above, and the inhibitory concentration 50% values for NR, MTF, and cell protein assays were 38.38, 36.27 and 32.03 μg/cm^3, respectively. This appeared to be the first report on the in vitro cytotoxicity of acetamiprid to non-mammalian vertebrate cells. Ultrastructural examination revealed that for the cells exposed to 60 μg/cm^3 acetamiprid for 48 h, their mitochondria were severely damaged with the cristae swelled up or disrupted, while their nuclei and rough endoplasmic reticlum （RER） appeared to be still normal. This suggests that mitochondria are possibly the primary target of acetamiprid.展开更多
In present days many types of materials are used to reduce the environmental pollution in the world which includes nanomaterials. Nanopesticides increase the efficacy, durability and reduction in the amount of active ...In present days many types of materials are used to reduce the environmental pollution in the world which includes nanomaterials. Nanopesticides increase the efficacy, durability and reduction in the amount of active constituent. The potential applications of nanotechnology in pesticides are quick decomposition in soil or plant, targeted delivery, apparent solubility and controlled release. In this communication the author reported a neonicatonoid insecticide called as Nano-acetamiprid and it is widely used to control fungal infections in different crops like cotton, leafy vegetables, citrus fruits, pome etc. The author reported a facile method i.e. a new Nano-acetamiprid for plant disease control and its subsequent characterization of encapsulated complex using polycaprolactone as an encapsulated agent. Nano-acetamiprid encapsulated particles were characterized by dynamic light scattering (DLS), ultraviolet spectroscopy and scanning electron microscopy (SEM). To ascertain the formation and the stability of nanoencapsulated acetamiprid pesticide, the maximum absorption spectra formulated at 421 nm and unformulated pesticide at 520 nm were observed. The size distribution was noted at 40 - 50 nm. The bioactivity study was conducted against various Aspergillus niger. The performance of nano particles was many fold times effective when compared to the original parental particles. The bio-assay of Nano-acetamiprid shows better results when compared to the normal commercial acetamiprid.展开更多
Honey bees are important pollinators and are essential in agriculture;as such they get exposed to a wide range of pesticides while foraging in contaminated fields or during the spray of chemical on crops. It is theref...Honey bees are important pollinators and are essential in agriculture;as such they get exposed to a wide range of pesticides while foraging in contaminated fields or during the spray of chemical on crops. It is therefore important to know the toxicity and evaluate the impacts of bees’ exposure to these molecules. Acetamiprid and cypermethrin are two pesticides widely used in Cameroon and other countries. The objective of this study was to determine the toxicity of acetamiprid and cypermethrin on the native subspecies of Apis mellifera L. in agricultural areas in Adamaoua-Cameroon and to evaluate the impact on honeybee foragers exposed to lethal and sublethal doses of these two insecticides. The results obtained in laboratory conditions show that acetamiprid and cypermethrin are toxic to A. mellifera. The symptoms of neurotoxicity and first mortality appear 15 min after the ingestion of the high concentrations and about 30 to 45 min after the inoculation of the pesticides through contact route and the mortality increases with the concentration and time. The LC50 of acetamiprid obtained after 24 h are respectively 5.26 ng/μl for the topical application and 4.70 μg/μl by the oral route. At the same time, the LC50 of cypermethrin are respectively 2.27 ng/μl for topical application and 2.68 ng/μl for oral toxicity. For a sustainable agriculture and beekeeping, it is, therefore, important to establish quality measures on these insecticides in the ecosystem and to set up a phyto-pharmacovigilance and awareness system to the population.展开更多
Acetamiprid is a novel neonicotinoid insecticide invented by Nippon Soda Co., Ltd.. To explore the possibility of acetamiprid as larvicide of mosquitoes, lethal and sublethal effects of acetamiprid on the larvae of ...Acetamiprid is a novel neonicotinoid insecticide invented by Nippon Soda Co., Ltd.. To explore the possibility of acetamiprid as larvicide of mosquitoes, lethal and sublethal effects of acetamiprid on the larvae of Culex pipiens pallens were studied by immersion method in the laboratory. The results indicated that the larvae of Culex pipiens pallens were sensitive to acetamiprid. The mortality of larvae peaked at 72 h after treatment. The 1st instar larvae was the most susceptible to acetamiprid, and the 4th instar larvae was the most tolerant to acetamiprid, the LC 50 values were 0.020 mg/L and 0.296 mg/L at 72 h after treatment, respectively. Sublethal concentrations of acetamiprid could delay the development of larvae and decrease the weight of pupa. We suggested that acetamiprid is a safe and effective substitute for the using larvicides of mosquitoes.展开更多
尽管新烟碱类杀虫剂具有种属特异性毒性,但流行病学研究表明暴露于啶虫脒(acetamiprid,ACE)导致儿童神经发育受损,动物实验表明产前暴露于ACE导致子代小鼠运动功能异常。目前对于新烟碱类杀虫剂对哺乳动物的神经毒性和机制知之甚少。本...尽管新烟碱类杀虫剂具有种属特异性毒性,但流行病学研究表明暴露于啶虫脒(acetamiprid,ACE)导致儿童神经发育受损,动物实验表明产前暴露于ACE导致子代小鼠运动功能异常。目前对于新烟碱类杀虫剂对哺乳动物的神经毒性和机制知之甚少。本研究基于多能干细胞体外神经分化模型,研究了0.5~50μmol·L^(-1)的ACE暴露对骨髓间充质干细胞的神经毒性效应潜能及毒性机制。首先对ACE与可能的作用靶点进行分子对接模拟,结果表明ACE与3种人烟碱型乙酰胆碱受体(nAChRs)以及人PPARγ受体均有一定的结合亲和性,虽然相互作用能低于其与昆虫AChBP受体的相互作用能,但可能通过作用于多个受体影响人体健康。在未造成显著细胞毒性浓度下,ACE暴露显著抑制鼠间充质干细胞(mesenchymal stem cells,MSCs)成神经分化的突触生成,ACE经鼠肝微粒体酶进行体外模拟代谢后该效应无显著变化。免疫荧光染色结果显示,50μmol·L^(-1)的ACE可显著抑制鼠神经元标志蛋白微管相关蛋白2(microtubule-associated protein 2,MAP2)的表达。0.5~50μmol·L^(-1)的ACE均可以显著提高细胞内活性氧水平。进一步用ACE作用于人源MSCs,对突触生成产生抑制作用,且在0.5~50μmol·L^(-1)暴露浓度范围内均刺激细胞钙瞬变,并呈剂量依赖性,诱导钙瞬变峰值比在1.25倍~1.5倍之间。本研究从细胞分化层面为流行病学发现和哺乳动物毒理学发现提供了机制解释,提示ACE可能干扰多能干细胞的谱系定向和命运决定。氧化应激及钙稳态失衡可能是ACE造成神经毒性的重要机制。须进一步筛查ACE损伤神经系统的敏感靶标,为该类农用化学品的风险管控提供科学依据。展开更多
基金supported by the National Key R&D Program of China(2022YFD1400300)the Open Fund of Key Laboratory of Integrated Pest Management on Crops in Northwestern Oasis,Ministry of Agriculture and Rural Affairs of China(KFJJ202204)the China Agriculture Research System(CARS-15-20)。
文摘Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii populations with different basal insecticide resistance levels,and evaluated the effects of basal insecticide resistance on the resistance development and cross-resistance,as well as differences in fitness.Under the same selection pressure,Yarkant A.gossypii(with low basal insecticide resistance)evolved resistance to sulfoxaflor and acetamiprid more quickly than Jinghe A.gossypii(with high basal insecticide resistance),and the evolution of A.gossypii resistance to sulfoxaflor developed faster than acetamiprid in both Yarkant and Jinghe,Xingjiang,China.The sulfoxaflor-resistant strains selected from Yarkant and Jinghe developed significant cross-resistance to acetamiprid,imidacloprid,thiamethoxam and pymetrozine;while the acetamiprid-resistant strains developed significant cross-resistance to sulfoxaflor,imidacloprid,thiamethoxam,pymetrozine,and chlorpyrifos.The relative fitness of A.gossypii decreased as the resistance to sulfoxaflor and acetamiprid developed.The relative fitness levels of the sulfoxaflor-resistant strains(Yarkant-SulR and Jinghe-SulR)were lower than those of the acetamipridresistant strains(Yarkant-AceR and Jinghe-AceR).In addition,the relative fitness levels of sulfoxaflor-and acetamiprid-resistant strains were lower in Jinghe than in Yarkant.In summary,basal insecticide resistance of A.gossypii and insecticide type affected the evolution of resistance to insecticides in A.gossypii,as well as cross-resistance to other insecticides.The sulfoxaflor-and acetamiprid-resistant A.gossypii strains had obvious fitness costs.The results of this work will contribute to the insecticide resistance management and integrated management of A.gossypii.
基金supported by the Natural Science Foundation Project of CQ CSTC,China(2010BB1138)the National Innovation Experiment Program for Undergraduate,China (091063530)
文摘Acetamiprid has a wide range of influence on physiological functions in mammals.The objective of this study was to examine the effect of acetamiprid on the reproductive function of male mice,and to study the role of oxidative stress in acetamiprid-induced damage to the testes.Fifty adult Kunmin male mice （25-30 g） were divided into five groups （n=10 per group）,i.e.,control,blank,acetamiprid alone,acetamiprid and vitamin E,and vitamin E alone.All groups were treated for 35 d.The results showed that acetamiprid significantly decreased the body weight and the weight of testosterone-responsive organs,such as the testis,epididymis,seminal vesicle,and prostate.Furthermore,acetamiprid also significantly reduced the serum testosterone concentration,and decreased sperm count,viability,motility,and the intactness of the acrosome （P〈0.05 for each parameter）.The mice treated with acetamiprid had damaged seminiferous tubules and Leydig cells based on the histological structure of testes;there was degeneration of the mitochondria and endoplasmic reticulum of Leydig cells.These deleterious effects of acetamiprid may be mediated by increasing oxidative stress,as acetamiprid increased malondialdehyde and nitric oxide in the testes,reduced the activity of catalase,glutathione peroxidase,superoxide dismutase,and activated p38.The concentration of acetamiprid in the testes was lower than that in liver,so did the concentrations of liver function tests,including aspartate transaminase （AST）,alanine transaminase （ALT） and alkaline phosphatase （ALP）,which suggest that male reproductive function may be affected through the indirect action of its metabolites.Vitamin E significantly ameliorated the effects of acetamiprid.We conclude that acetamiprid damages male reproductive function through inducing oxidative stress in the testes.
基金The project was supported by National Natural Science Foundation of China (No. 30370048).
文摘Objective To investigate how acetamiprid, a new insecticide, affects the activity of superoxide dismutase （SOD）, catalase （CAT）, and ATPase and the SOD isozyme patterns in two G-bacteria, E. coli K12 anti Pse.FH2, and one G^＋ bactemm, B. subtilis. Methods The SOD, CAT, and ATPase specific activities of cell lysates were determined spectrophotometrically at 550 nm, 240 nm, and 660 nm, respectively, with kits A001, A016, and A007. SOD isozyme patterns were detected by native PAGE analysis. Results SOD and CAT activities in the tested bacteria increased significantly in a concentration-dependent manner after different concentrations of acetamiprid were applied. The activity of SOD in B. subtilis and Pse.FH2 was stimulated and reached the highest level after treatment with 100 mg/L acetamiprid for 0.5 h. For Pse.FH2, there was another stimulation of SOD activity after acetamiprid application for about 8.0 h and the second stimulation was stronger than the first. The stimulation by acetamiprid showed a relative lag for E. coli K12. Acetamiprid seemed to exhibit a similar effect on CAT activity of the two G bacteria and had an evident influence on ATPase activity in the three bacteria within a relatively short period. Only one SOD isozyme was detectable in Pse.FH2 and B. subtilis, while different isozyme compositions in E. coli could be detected by native PAGE analysis. Conclusion Acetamiprid causes a certain oxidative stress on the three bacteria which may not only elevate SOD and CAT activities but also generate new SOD isozymes to antagonize oxidative stress. However, this oxidative stress lasts for a relatively short time and does not cause a long-term damage.
基金The National Natural Science Foundation of China（No. 30370048 30570053）
文摘An aerobic bacterium, capable of degrading the new chloronicotine pesticide acetamiprid, was isolated from the sludge of pesticide factory after successive enrichment cultures and named strain FH2 which is a Gram-negative, rod-shaped, obligate aerobic organism with （（0.5-0.7）×（l.5-3.0））μm of cell size and with monotrichous flagellum. It was identified as a member of Pseudomonas sp. based on morphology, physio-biochemical properties, Biolog GN2, 16S rDNA sequence and phylogenetic characteristic analysis. The isolate could grow optimally at pH 7.0 and 30℃ in acetamiprid-mineral medium with 800 mg/L concentration. About 53.3% acetamiprid was degraded by strain FH2 after incubation for 14 d in acetamiprid-mineral medium and nearly 96.7% degraded when incubated in acetamiprid-yeast mineral medium at 30℃ for 14 d. This paper describes phylogenetic and degradation characterization of a pure bacterium being able to mineralize acetamiprid for the first time.
文摘The in vitro acute cytotoxicity of the neonicotinoid insecticide acetamiprid to FG cell line, derived from the gill of flounder Paralichthys olizaceus, was tested by the three widely used endpoint bioassays-neutral red （NR） assay, tetrazolium （MTT） assay and cell protein assay. It was found that acetamiprid was increasingly toxic to FG cells at concentrations of 1 μg/cm^3 or above, and the inhibitory concentration 50% values for NR, MTF, and cell protein assays were 38.38, 36.27 and 32.03 μg/cm^3, respectively. This appeared to be the first report on the in vitro cytotoxicity of acetamiprid to non-mammalian vertebrate cells. Ultrastructural examination revealed that for the cells exposed to 60 μg/cm^3 acetamiprid for 48 h, their mitochondria were severely damaged with the cristae swelled up or disrupted, while their nuclei and rough endoplasmic reticlum （RER） appeared to be still normal. This suggests that mitochondria are possibly the primary target of acetamiprid.
文摘In present days many types of materials are used to reduce the environmental pollution in the world which includes nanomaterials. Nanopesticides increase the efficacy, durability and reduction in the amount of active constituent. The potential applications of nanotechnology in pesticides are quick decomposition in soil or plant, targeted delivery, apparent solubility and controlled release. In this communication the author reported a neonicatonoid insecticide called as Nano-acetamiprid and it is widely used to control fungal infections in different crops like cotton, leafy vegetables, citrus fruits, pome etc. The author reported a facile method i.e. a new Nano-acetamiprid for plant disease control and its subsequent characterization of encapsulated complex using polycaprolactone as an encapsulated agent. Nano-acetamiprid encapsulated particles were characterized by dynamic light scattering (DLS), ultraviolet spectroscopy and scanning electron microscopy (SEM). To ascertain the formation and the stability of nanoencapsulated acetamiprid pesticide, the maximum absorption spectra formulated at 421 nm and unformulated pesticide at 520 nm were observed. The size distribution was noted at 40 - 50 nm. The bioactivity study was conducted against various Aspergillus niger. The performance of nano particles was many fold times effective when compared to the original parental particles. The bio-assay of Nano-acetamiprid shows better results when compared to the normal commercial acetamiprid.
文摘Honey bees are important pollinators and are essential in agriculture;as such they get exposed to a wide range of pesticides while foraging in contaminated fields or during the spray of chemical on crops. It is therefore important to know the toxicity and evaluate the impacts of bees’ exposure to these molecules. Acetamiprid and cypermethrin are two pesticides widely used in Cameroon and other countries. The objective of this study was to determine the toxicity of acetamiprid and cypermethrin on the native subspecies of Apis mellifera L. in agricultural areas in Adamaoua-Cameroon and to evaluate the impact on honeybee foragers exposed to lethal and sublethal doses of these two insecticides. The results obtained in laboratory conditions show that acetamiprid and cypermethrin are toxic to A. mellifera. The symptoms of neurotoxicity and first mortality appear 15 min after the ingestion of the high concentrations and about 30 to 45 min after the inoculation of the pesticides through contact route and the mortality increases with the concentration and time. The LC50 of acetamiprid obtained after 24 h are respectively 5.26 ng/μl for the topical application and 4.70 μg/μl by the oral route. At the same time, the LC50 of cypermethrin are respectively 2.27 ng/μl for topical application and 2.68 ng/μl for oral toxicity. For a sustainable agriculture and beekeeping, it is, therefore, important to establish quality measures on these insecticides in the ecosystem and to set up a phyto-pharmacovigilance and awareness system to the population.
文摘Acetamiprid is a novel neonicotinoid insecticide invented by Nippon Soda Co., Ltd.. To explore the possibility of acetamiprid as larvicide of mosquitoes, lethal and sublethal effects of acetamiprid on the larvae of Culex pipiens pallens were studied by immersion method in the laboratory. The results indicated that the larvae of Culex pipiens pallens were sensitive to acetamiprid. The mortality of larvae peaked at 72 h after treatment. The 1st instar larvae was the most susceptible to acetamiprid, and the 4th instar larvae was the most tolerant to acetamiprid, the LC 50 values were 0.020 mg/L and 0.296 mg/L at 72 h after treatment, respectively. Sublethal concentrations of acetamiprid could delay the development of larvae and decrease the weight of pupa. We suggested that acetamiprid is a safe and effective substitute for the using larvicides of mosquitoes.
文摘尽管新烟碱类杀虫剂具有种属特异性毒性,但流行病学研究表明暴露于啶虫脒(acetamiprid,ACE)导致儿童神经发育受损,动物实验表明产前暴露于ACE导致子代小鼠运动功能异常。目前对于新烟碱类杀虫剂对哺乳动物的神经毒性和机制知之甚少。本研究基于多能干细胞体外神经分化模型,研究了0.5~50μmol·L^(-1)的ACE暴露对骨髓间充质干细胞的神经毒性效应潜能及毒性机制。首先对ACE与可能的作用靶点进行分子对接模拟,结果表明ACE与3种人烟碱型乙酰胆碱受体(nAChRs)以及人PPARγ受体均有一定的结合亲和性,虽然相互作用能低于其与昆虫AChBP受体的相互作用能,但可能通过作用于多个受体影响人体健康。在未造成显著细胞毒性浓度下,ACE暴露显著抑制鼠间充质干细胞(mesenchymal stem cells,MSCs)成神经分化的突触生成,ACE经鼠肝微粒体酶进行体外模拟代谢后该效应无显著变化。免疫荧光染色结果显示,50μmol·L^(-1)的ACE可显著抑制鼠神经元标志蛋白微管相关蛋白2(microtubule-associated protein 2,MAP2)的表达。0.5~50μmol·L^(-1)的ACE均可以显著提高细胞内活性氧水平。进一步用ACE作用于人源MSCs,对突触生成产生抑制作用,且在0.5~50μmol·L^(-1)暴露浓度范围内均刺激细胞钙瞬变,并呈剂量依赖性,诱导钙瞬变峰值比在1.25倍~1.5倍之间。本研究从细胞分化层面为流行病学发现和哺乳动物毒理学发现提供了机制解释,提示ACE可能干扰多能干细胞的谱系定向和命运决定。氧化应激及钙稳态失衡可能是ACE造成神经毒性的重要机制。须进一步筛查ACE损伤神经系统的敏感靶标,为该类农用化学品的风险管控提供科学依据。
