Disodium Fumarate Alleviates Endoplasmic Reticulum Stress, Mitochondrial Damage, and Oxidative Stress Induced by the High-Concentrate Diet in the Mammary Gland Tissue of Hu Sheep.

Disodium Fumarate Alleviates Endoplasmic Reticulum Stress, Mitochondrial Damage, and Oxidative Stress Induced by the High-Concentrate Diet in the Mammary Gland Tissue of Hu Sheep.
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富马酸二钠减轻湖羊乳腺组织高精饲料引起的内质网应激、线粒体损伤和氧化应激

DOI:
10.3390/antiox12020223
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发表时间:
2023-01-18
期刊:
Antioxidants (Basel, Switzerland)
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长期饲喂高精料(HC)可降低瘤胃pH值,诱发亚急性瘤胃酸中毒(SARA),导致反刍动物乳腺组织损伤。富马酸二钠增强了瘤胃缓冲作用,减轻了HC日粮引起的瘤胃pH值下降。因此,本研究旨在探讨富马酸二钠能否缓解高精料日粮诱导的湖羊乳腺组织内质网应激、线粒体损伤和氧化应激。本试验选用18只哺乳中期湖羊,随机分为3组,分别饲喂低精料日粮(LC)、高精料日粮(HC)和富马酸二钠(AHC)日粮。每只绵羊每天额外给予10 g富马酸二钠。实验持续了8周。试验结束后,收集瘤胃液、血液和乳腺组织。结果表明,与对照组相比,HC组能降低瘤胃pH,pH低于5.6的时间超过3 h,且HC组血液和瘤胃液中LPS含量显著高于对照组。这表明HC日粮诱导湖羊SARA。然而,在HC日粮中添加富马酸二钠提高了瘤胃pH值,降低了血液和瘤胃液中LPS的含量。与低钙日粮相比,高钙日粮能提高乳腺组织中Ca ~(2+)含量。而AHC日粮则降低了Ca ~(2+)含量。HC饮食通过增加GRP 78、CHOP、PERK、ATF 6和IRE 1 α的mRNA和蛋白表达诱导乳腺组织中的ER应激。HC饮食还激活了IP 3R-VDAC 1-MCU通道,并通过抑制线粒体融合和促进线粒体分裂导致线粒体损伤,而富马酸二钠可以减轻这些变化。此外,富马酸二钠通过激活Nrf 2信号传导和减少乳腺组织中的ROS产生来缓解HC饲料诱导的氧化应激。总之,以10 g/羊的日剂量补充富马酸二钠通过维持瘤胃pH高于6和降低瘤胃液和血液中的LPS浓度来增强瘤胃缓冲。这种反应避免了观察到的负面影响,非补充羊饲喂高浓缩饲料,涉及内质网应激,氧化应激,和线粒体损伤湖羊乳腺组织。
The long-term feeding of the high-concentrate diet (HC) reduced rumen pH and induced subacute rumen acidosis (SARA), leading to mammary gland tissue damage among ruminants. Disodium fumarate enhanced rumen bufferation and alleviated a decrease in rumen pH induced by the HC diet. Therefore, the purpose of this study was to investigate whether disodium fumarate could alleviate endoplasmic reticulum (ER) stress, mitochondrial damage, and oxidative stress induced by the high-concentrate diet in the mammary gland tissue of Hu sheep. In this study, 18 Hu sheep in mid-lactation were randomly divided into three groups: one fed with a low-concentrate diet (LC) diet, one fed with a HC diet, and one fed with a HC diet with disodium fumarate (AHC). Each sheep was given an additional 10 g of disodium fumarate/day. The experiment lasted for eight weeks. After the experiment, rumen fluid, blood, and mammary gland tissue were collected. The results show that, compared with the LC diet, the HC diet could reduce rumen pH, and the pH below 5.6 was more than 3 h, and the LPS content of blood and rumen fluid in HC the diet was significantly higher than in the LC diet. This indicates that the HC diet induced SARA in Hu sheep. However, the supplementation of disodium fumarate in the HC diet increased the rumen pH and decreased the content of LPS in blood and rumen fluid. Compared with the LC diet, the HC diet increased Ca2+ content in mammary gland tissue. However, the AHC diet decreased Ca2+ content. The HC diet induced ER stress in mammary gland tissue by increasing the mRNA and protein expressions of GRP78, CHOP, PERK, ATF6, and IRE1α. The HC diet also activated the IP3R-VDAC1-MCU channel and lead to mitochondrial damage by inhibiting mitochondrial fusion and promoting mitochondrial division, while disodium fumarate could alleviate these changes. In addition, disodium fumarate alleviated oxidative stress induced by the HC diet by activating Nrf2 signaling and reducing ROS production in mammary gland tissue. In conclusion, the supplementation of disodium fumarate at a daily dose of 10 g/sheep enhanced rumen bufferation by maintaining the ruminal pH above 6 and reduced LPS concentration in ruminal fluid and blood. This reaction avoided the negative effect observed by non-supplemented sheep that were fed with a high-concentrate diet involving endoplasmic reticulum stress, oxidative stress, and mitochondrial damage in the mammary gland tissue of Hu sheep.
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