Pesticides and plastics bring convenience to agriculture and life, but also bring residual pollution in the environment. Emamectin benzoate (EMB) is the most popular pesticide at present. The harm of microplastics (MPs) to water and aquatic organisms is gradually increasing, and the possibility that it appears synchronously with various pesticides increases. However, the damage of EMB and MPs to the carp midgut and its mechanism have not been clarified. Therefore, based on the EMB or/and MPs exposure models, this study explored the mechanism of midgut injury through transcriptomics, immunofluorescence, western blot methods, and so on. Studies and showed that EMB or MPs exposure caused cilia shortening, lysosome damage, and ROS overproduction, which led to Fe content increase, GSH/GSSG system disorder, lipid peroxidation, and ferroptosis. This process further led to the down-regulation of Cx43, Occludin, Claudin, and ZO-1, which further caused barrier damage, immune-related genes (immunoglobulin, IFN-γ) decrease and inflammation-related genes (TNF-α, IL-1β) increase. Combined exposure was more significant than that of single exposure, and the addition of EN6 and NAC proved that lysosome/ROS/ferroptosis regulated these midgut damages. In conclusion, EMB or/and MPs exposure induce tight junction disorder, immune disorder and inflammation in carp midgut through the lysosome/ROS/ferroptosis pathway.

中文翻译：

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甲维盐与微塑料联合暴露通过溶酶体/ROS/铁死亡途径诱导鲤鱼中肠紧密连接紊乱、免疫紊乱和炎症

农药和塑料给农业和生活带来便利的同时，也给环境带来残留污染。甲维盐苯甲酸酯（EMB）是目前最流行的农药。微塑料（MPs）对水体和水生生物的危害逐渐加大，且与各种农药同步出现的可能性增大。但EMB和MPs对鲤鱼中肠的损伤及其机制尚不清楚。因此，本研究基于EMB或/和MPs暴露模型，通过转录组学、免疫荧光、蛋白质印迹等方法探讨中肠损伤的机制。研究表明，EMB或MPs暴露会导致纤毛缩短、溶酶体损伤和ROS过量产生，从而导致Fe含量增加、GSH/GSSG系统紊乱、脂质过氧化和铁死亡。这一过程进一步导致Cx43、Occludin、Claudin、ZO-1的下调，进一步引起屏障损伤、免疫相关基因（免疫球蛋白、IFN-γ）减少和炎症相关基因（TNF-α、IL） -1β）增加。联合暴露比单一暴露更显着，EN6和NAC的添加证明溶酶体/ROS/铁死亡调节这些中肠损伤。总之，EMB或/和MPs暴露通过溶酶体/ROS/铁死亡途径诱导鲤鱼中肠紧密连接紊乱、免疫紊乱和炎症。