Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by Fusarium strains that is harmful to the intestinal health of animals and is widely present in contaminated crops. The objective of this study was to investigate the potential therapeutic target of ZEN-induced jejunal damage in weaned gilts. Sixteen weaned gilts either received a basal diet or a basal diet supplemented with 3.0 mg/kg ZEN in a 32-d experiment. The results showed that ZEN at the concentration of 3.0 mg/kg diet activated the inflammatory response and caused oxidative stress of gilts (P < 0.05). ZEN exposure resulted in the upregulation (P < 0.05) of the Exchange protein directly activated by the cAMP 1/Ras-related protein1/c-Jun N-terminal kinase (Epac1/Rap1/JNK) signaling pathway in the jejunum of gilts in vivo and in the intestinal porcine epithelial cells in vitro. The cell viability, EdU-positive cells, and the mRNA expression of B-cell lymphoma-2 (Bcl-2) were decreased, whereas the reactive oxygen species production and the mRNA expressions of Bcl-2-associated X (Bax) and Cysteine-aspartic acid protease 3 (Caspase3) were increased (P < 0.05) by ZEN. However, ZEN increased the mRNA expression of Bcl-2 and decreased the mRNA expressions of Bax and caspase3 (P < 0.05) after the Epac1 was blocked. These results collectively indicated that a 3.0 mg ZEN /kg diet induced jejunal damage via the Epac1/Rap1/JNK signaling pathway.

中文翻译：

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玉米赤霉烯酮通过 Epac1/Rap1/JNK 通路对断奶后备母猪空肠的影响


玉米赤霉烯酮 （ZEN） 是由镰刀菌菌株产生的一种非甾体雌激素霉菌毒素，对动物的肠道健康有害，广泛存在于受污染的作物中。本研究的目的是探讨 ZEN 诱导的断奶后备母猪空肠损伤的潜在治疗靶点。在 32 天实验中，16 头断奶后备母猪接受基础日粮或补充 3.0 mg/kg ZEN 的基础日粮。结果表明，日粮中3.0 mg/kg的ZEN激活了后备母猪的炎症反应，引起了后备母猪的氧化应激（P < 0.05）。ZEN 暴露导致 cAMP 1/Ras 相关蛋白 1/c-Jun N 末端激酶 （Epac1/Rap1/JNK） 信号通路直接激活的交换蛋白上调 （P < 0.05） 在后备母猪体内空肠和体外肠猪上皮细胞中。ZEN 降低细胞活力、EdU 阳性细胞和 B 细胞淋巴瘤-2 （Bcl-2） mRNA 表达，而 ZEN 增加活性氧产生以及 Bcl-2 相关 X （Bax） 和半胱氨酸-天冬氨酸蛋白酶 3 （Caspase3） 的 mRNA 表达 （P < 0.05）。阻断 Epac1 后，ZEN 增加 Bcl-2 的 mRNA 表达，降低 Bax 和 caspase3 的 mRNA 表达 （P < 0.05）。这些结果共同表明，3.0 mg ZEN /kg 饮食通过 Epac1/Rap1/JNK 信号通路诱导空肠损伤。