基于神经多受体复合物新视角的杀虫剂抗药性
New perspectives on insecticide toxicology and resistance based on neural multireceptor complexes
万岩然1** 王茂源1 陈可为1 钱康华2 杨浩岚2 吴青君2***
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DOI：10.7679/j.issn.20951353.2026.105
作者单位：1. 河北农业大学植物保护学院，保定 071000；2. 中国农业科学院蔬菜花卉研究所， 蔬菜生物育种全国重点实验室，北京 100081
中文关键词：神经多受体复合物；神经毒性杀虫剂；信号串扰；交互抗性
英文关键词：neural multireceptor complexes; neurotoxic insecticides; signal cross-talk; cross-resistance
中文摘要：神经毒性杀虫剂对全球粮食安全和公共卫生有重要作用，但其广泛应用已引发害虫抗性问题。传统靶点突变与代谢解毒理论已阐明多种抗性机制，但对不同作用机理杀虫剂间的非预期交互抗性、功能代偿等复杂现象，经典“单一靶点”研究范式解释力不足，提示昆虫神经系统存在比现有认知更复杂的靶标组织模式与调控网络。脊椎动物神经研究显示，神经受体可组装为功能性“神经多受体复合物”，通过变构调节、信号串扰协同调控神经元功能。鉴于神经系统进化高度保守，本研究将该理论引入昆虫毒理学与抗药性研究，认为神经递质受体通过蛋白质相互作用组装为超分子复合物，协同调控神经元功能。本研究分析典型抗药性案例，构建昆虫抗药性新假说，整合了昆虫体内存在功能性神经多受体复合物并介导抗药性的间接证据：跨靶标交互抗性及神经受体功能代偿。构建了基于神经多受体复合物抗性理论框架，提出昆虫神经系统中nAChR、VGSC、GABAR、GluR等关键杀虫剂靶点形成功能整合的受体网络，针对任一节点的持续选择压力不仅会引发该节点适应性改变，还会通过复合物内相互作用将影响传递至其他节点，最终形成复杂广谱抗性表型。“神经多受体复合物”理论为理解杀虫剂作用机制与抗性演化提供了全新视角，将研究范式从“单一分子”提升至“系统网络”层面，既为传统模型难以解释的非预期交互抗性和功能代偿提供了分子框架，也为未来杀虫剂研发开辟了新方向，对制定科学的抗性治理策略具有重要理论指导意义与应用前景。
英文摘要：Neurotoxic insecticides play vital roles in safeguarding global food security and public health, however, their widespread application has triggered the development of pest resistance. Multiple resistance mechanisms have been clarified using the theories of conventional target-site mutation and metabolic detoxification. Nevertheless, the classical "single-target" research paradigm lacks explanatory power for complex phenomena, such as unintended cross-resistance and functional compensation among insecticides with disparate modes of action. This indicates that the insect nervous system possesses more sophisticated target organization patterns and regulatory networks than are currently understood. Neuroscientific research on vertebrates has demonstrated that neural receptors can assemble into functional "multineuroreceptor complexes", which collaboratively regulate neuronal functions through allosteric modulation and signal crosstalk. Given the high evolutionary conservation of nervous systems across species, the present study introduces this theory into insect toxicology and insecticide resistance research. We hypothesize that neurotransmitter receptors assemble into supramolecular complexes via protein- protein interactions to cooperatively govern neuronal activity. By analyzing representative cases of insecticide resistance, this work establishes a novel hypothesis for insect resistance, assembling indirect evidence supporting the existence of functional multineuroreceptor complexes mediating resistance in insects, namely cross-target cross-resistance and functional compensation of neural receptors. A theoretical framework of resistance rooted in the multineuroreceptor complex is postulated: Key insecticide targets within the insect nervous system, including nAChRs, VGSCs, GABARs and GluRs, form an integrative functional receptor network. Continuous selection pressure acting on any single node of this network induces adaptive alterations at that node, the impacts of which propagate to other nodes via intramolecular interactions within the complexes, ultimately generating complex broad-spectrum resistance phenotypes. The multineuroreceptor complex theory offers an innovative perspective for deciphering insecticide modes of action and the evolution of resistance, elevating the research paradigm from the "single-molecule" level to the “systematic network” level. It furnishes a molecular framework to interpret unexpected cross-resistance and functional compensation that cannot be explained by traditional models, pioneers new avenues for future insecticide development, and has important theoretical significance and prospects for the formulation and application of scientific strategies to manage resistance.