Gan Fang, Hou Lili, Zhou Yajiao, Liu Yunhuan, Huang Da, Chen Xingxiang, Huang Kehe
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
Environ Toxicol. 2017 Oct;32(10):2277-2286. doi: 10.1002/tox.22443. Epub 2017 Jul 12.
Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin and immunotoxin in animals and humans. This research was conducted to evaluate whether endoplasmic reticulum (ER) stress, MAPK signaling pathway and autophagy were induced by OTA in kidney and spleen of pigs. Twenty-seven crossbred pigs randomly allocated to 3 groups were fed for 42 days ad libitum a basal diet without (Con group, 0.00 μg OTA/kg) and with supplementation of OTA at 400 (OTA-L group) and 800 μg/kg (OTA-H group). From each group, 6 pigs were randomly selected for blood collection on days 0, 21, and 42 and 3 pigs were randomly selected for tissue collection on day 42. The results showed that OTA at 400 and 800 μg/kg diets significantly increased OTA concentrations in serum and kidney and spleen induced the histopathological lesions of kidney and spleen, decreased TCR-stimulated T lymphocyte viabilities and IL-2 concentration, increased TNF-α concentration, and decreased T-AOC levels. OTA increased glucose regulated protein 78, p38, and ERK1/2 phosphorylation, and LC3 II and Atg5 protein expression in kidney and spleen of pigs. These results provide new insights into the relationship between OTA and ER stress, p38 and ERK1/2 MAPK signaling pathway and autophagy in pigs.
赭曲霉毒素A（OTA）是一种在食品和饲料中广泛存在的霉菌毒素，对动物和人类具有很强的肾毒性和免疫毒性。本研究旨在评估OTA是否会在猪的肾脏和脾脏中诱导内质网（ER）应激、丝裂原活化蛋白激酶（MAPK）信号通路和自噬。将27头杂交猪随机分为3组，自由采食基础日粮42天，其中一组不添加OTA（对照组，0.00μg OTA/kg），另外两组分别添加400（OTA-L组）和800μg/kg（OTA-H组）的OTA。在第0、21和42天，从每组中随机选取6头猪采血，在第42天，从每组中随机选取3头猪采集组织。结果表明，日粮中添加400和800μg/kg的OTA显著提高了血清、肾脏和脾脏中的OTA浓度，诱导了肾脏和脾脏的组织病理学损伤，降低了T细胞受体刺激的T淋巴细胞活力和白细胞介素-2浓度，提高了肿瘤坏死因子-α浓度，并降低了总抗氧化能力水平。OTA增加了猪肾脏和脾脏中葡萄糖调节蛋白78、p38和细胞外信号调节激酶1/2（ERK1/2）的磷酸化水平，以及微管相关蛋白1轻链3Ⅱ（LC3Ⅱ）和自噬相关蛋白5（Atg5）的蛋白表达。这些结果为OTA与猪体内ER应激、p38和ERK1/2 MAPK信号通路以及自噬之间的关系提供了新的见解。
