Abstract：
As primary flavonoids extracted from citrus fruits, hesperidin has been attracting attention widely for its capacity to act as antioxidants that are able to scavenge free radicals and reactive oxygen species (ROS). Many factors have made oxidative stress a risk factor for the occurrence of intestinal barrier injury, which is a serious health threat to human beings. However, little data are available regarding the underlying mechanism of hesperidin alleviating intestinal injury under oxidative stress. Recently, endoplasmic reticulum (ER) mitochondria contact sites (ERMCSs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and Ca2+ transport. In our experiment, 24 piglets were randomly divided into 4 groups. Piglets in the diquat group and hesperidin + diquat group received an intraperitoneal injection of diquat (10 mg/kg), while piglets in the hesperidin group and hesperidin + diquat group received hesperidin (300 mg/kg) with feed. The results indicated that hesperidin alleviated growth restriction and intestinal barrier injury in piglets compared with the diquat group. Hesperidin ameliorated oxidative stress and restored antioxidant capacity under diquat exposure. The mitochondrial dysfunction was markedly alleviated via hesperidin versus diquat group. Meanwhile, hesperidin alleviated ER stress and downregulated the PERK pathway. Furthermore, hesperidin prevented the disorder of ERMCSs by downregulating the level of ERMCS proteins, decreasing the percentage of mitochondria with ERMCSs/total mitochondria and the ratio of ERMCSs length/mitochondrial perimeter. These results suggested hesperidin could alleviate ERMCS disorder and prevent mitochondrial dysfunction, which subsequently decreased ROS production and alleviated intestinal barrier injury of piglets under oxidative stress.
摘要：
作为从柑橘类水果中提取的主要类黄酮，橙皮苷作为能够清除自由基和活性氧（ROS）的抗氧化剂的能力已引起广泛关注。许多因素使氧化应激成为肠屏障损伤发生的危险因素,这是对人类健康的严重威胁。然而,关于橙皮苷减轻氧化应激下肠损伤的潜在机制的数据很少。最近,内质网(ER)线粒体接触位点(ERMCSs)引起了越来越多学者的关注,参与线粒体动力学和Ca2+转运。在我们的实验中,24只仔猪随机分为4组。敌快组及橙皮苷+敌快组均腹腔注射10mg/kg,而橙皮苷组和橙皮苷+敌草快组的仔猪在饲料中接受橙皮苷(300mg/kg)。结果表明,橙皮苷对仔猪生长受限和肠屏障损伤的影响较好。橙皮苷改善了敌草快暴露下的氧化应激并恢复了抗氧化能力。与敌快组相比，橙皮苷组明显减轻了线粒体功能障碍。同时,橙皮苷减轻内质网应激并下调PERK通路。此外，橙皮苷通过下调ERMCS蛋白的水平来预防ERMCSs的紊乱，降低ERMCSs/总线粒体的线粒体百分比和ERMCSs长度/线粒体周长的比率。这些结果表明橙皮苷可以缓解ERMCS障碍和防止线粒体功能障碍。随后减少了ROS的产生，减轻了氧化应激下仔猪的肠屏障损伤。
