基于神经-内分泌-免疫网络的微囊藻毒素免疫毒性研究

随着湖泊富营养化和蓝藻水华频繁爆发，微囊藻毒素（microcystins，简称MCs）对水环境危害及人类健康威胁已成为全球关注的重大环境问题之一。最新研究结果表明，MCs具有免疫毒性，同时还是潜在的雌激素样内分泌干扰物，但有关MCs的内分泌干扰作用对免疫毒性影响的研究还很缺乏。针对此，本研究拟采用环境浓度MC-LR长期暴露模拟自然条件染毒，选取斑马鱼为研究对象，以神经-内分泌-免疫调节网络为切入点，利用形态学、生化检测、实时定量PCR及转录组学等多种手段，从MC-LR的直接免疫毒性和基于神经内分泌网络对免疫的间接调控两个方面，结合组织学，非特异性免疫，特异性免疫和免疫信号作用通路多个层面的研究系统阐明MC-LR的免疫毒性作用及其调控通路。研究的结果可以拓展人们对MC-LR毒性的认知，同时可为评估MCs对水环境的生态风险及人类健康的潜在威胁提供有力的数据支撑。

With the frequent occurrence of lake eutrophication and cyanobacteria bloom, microcystins (MCs) have become one of the most important environmental problems all over the world. The latest research results show that MC-LR has immunotoxicity, which is also a potential estrogen-like endocrine disruptor. However, the relationship between immunotoxicity and endocrine-toxicity induced by MCs remains to be elaborated. In light of the above, zebrafish are chosen as experiment animal in this project. Through the exposure experiment of low dose of MC-LR, this project aims to investigate the effects of MC-LR on the histology, non-specific immunity, specific immunity and immune signaling pathway in the immune organ of zebrafish by methods of morphology, biochemical detection, fluorescence quantitative PCR and transcriptom, etc., and to evaluate the relationship between its estrogen-like effects and immunotoxicity in the basis of neuro-endocrin-immunoregulatory network. The results will try to provide scientific basis for the risk management and health security of ecological environment to MCs pollution and also for the evaluation of the potential harmful effects of MCs on human health.