Curcumin Alleviates IUGR Jejunum Damage by Increasing Antioxidant Capacity through Nrf2/Keap1 Pathway in Growing Pigs
Curcumin Alleviates IUGR Jejunum Damage by Increasing Antioxidant Capacity through Nrf2/Keap1 Pathway in Growing Pigs
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DOI：
10.3390/ani10010041
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
E. Yan;Jiaqi Zhang;H. Han;Jiamin Wu;Zhending Gan;C. Wei;Lili Zhang;Chao Wang;Tian Wang
中科院分区：
文献类型：
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作者：
E. Yan;Jiaqi Zhang;H. Han;Jiamin Wu;Zhending Gan;C. Wei;Lili Zhang;Chao Wang;Tian Wang
胎儿宫内生长迟缓（IUGR）通常定义为胎儿生长低于胎龄的第10百分位数，并导致妊娠期间胎儿和/或其器官的生长和发育受损。IUGR不仅对出生后的生长和长期健康有永久性影响，而且还导致高胎儿死亡率和发病率。最近的研究表明，IUGR可引起仔猪空肠损伤。空肠不仅是消化吸收营养物质的主要器官，而且是机体的免疫器官。但目前还没有发现有效缓解IUGR猪空肠损伤和氧化应激的方法，近年来研究发现姜黄素（CUR）可能是一种有效、安全的调节体内氧化应激的饲料添加剂。结果表明，在基础日粮中添加200 mg/kg姜黄素可提高IUGR生长猪空肠抗氧化能力，减轻IUGR生长猪空肠损伤。因此，姜黄素作为饲料添加剂具有一定的经济价值。摘要本研究旨在探讨姜黄素对胎儿宫内发育迟缓（IUGR）空肠损伤的影响。选用24头IUGR和12头正常出生体重（NBW）的杜长大三元杂交（杜×长×大白色）母猪，于断奶时（26日龄）随机分为3组：IUGR组、NBW组和IUGR + CUR组，分别在26 ~ 115日龄饲粮中添加姜黄素0 mg/kg（NBW）、0 mg/kg（IUGR）和200 mg/kg（IUGR + CUR）。结果表明，日粮中添加200 mg/kg姜黄素可显著提高IUGR猪空肠组织中总超氧化物歧化酶（T-SOD）活性，降低丙二醛（MDA）含量（p < 0.05）。实时荧光定量PCR结果显示，IUGR + CUR组NF-E2相关因子2（Nrf 2）基因表达显著增加，（p < 0.05），并增加谷氨酸-半胱氨酸连接酶催化亚基（GCLC）、超氧化物歧化酶1（SOD 1）、谷氨酸-半胱氨酸连接酶修饰亚基（GCLM）、与IUGR组比较，NQO 1 mRNA表达显著升高（P < 0.05）。Western blot结果显示，在日粮中添加200 mg/kg姜黄素显著增加了Nrf 2和NQO 1的蛋白水平。与IUGR组相比，IUGR + CUR组仔猪血清肿瘤坏死因子α（TNFα）、白细胞介素6（IL 6）和干扰素γ（IFNγ）水平显著降低（p < 0.05），白细胞介素2（IL 2）水平显著升高（p < 0.05）。饮食补充200 mg/kg姜黄素显著降低半胱氨酸天冬氨酸特异性蛋白酶3（caspase 3）、BCL 2相关X蛋白（bax）、B细胞CLL/淋巴瘤2（bcl 2）和热休克蛋白70（hsp 70）mRNA表达，并增加闭合蛋白（occlin）mRNA表达（p < 0.05）。结论：日粮中添加200 mg/kg姜黄素可通过Nrf 2/Keap 1途径减轻IUGR生长猪空肠损伤。
Simple Summary Intrauterine growth retardation (IUGR) is usually defined as fetal growth below the 10th percentile for gestational age and results in impaired growth and development of the fetus and/or its organs during gestation. IUGR not only has a permanent effect on postnatal growth and long-term health, but also results in high fetal mortality and morbidity. Recent results have demonstrated that IUGR can cause jejunum damage in piglets. The jejunum is not only the main organ for the digestion and absorption of nutrients, but also an immune organ in the body. However, few effective methods to alleviate jejunum damage and oxidative stress in IUGR pigs have been found. In recent years, studies have found that curcumin (CUR) may be an effective and safe feed additive for regulating oxidative stress in the body. Our results indicated that dietary added 200 mg/kg curcumin to the basal diet can increase the antioxidant capacity of the IUGR growing pigs, jejunum and alleviate the damage in jejunum of the IUGR growing pigs. Therefore, the use of curcumin as a feed additive has certain economic value. Abstract The purpose of this study was to explore the effects of curcumin on IUGR jejunum damage. A total of 24 IUGR and 12 normal-birth weight (NBW) female crossbred (Duroc × Landrace × Large White) piglets were randomly assigned into three groups at weaning (26 days): IUGR group, NBW group, and IUGR + CUR group, which were fed diets containing 0 mg/kg (NBW), 0 mg/kg (IUGR) and 200 mg/kg (IUGR + CUR) curcumin from 26 to 115 days of age. Results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the total superoxide dismutase (T-SOD) activity and decreased the malondialdehyde (MDA) content in the jejunum of IUGR pigs (p < 0.05). Results of real-time PCR showed that the IUGR + CUR group significantly increased the gene expression of NF-E2-related factor 2 (Nrf2) (p < 0.05), and increased the glutamate-cysteine ligase catalytic subunit (GCLC), superoxide dismutase 1 (SOD1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA expression compared with the IUGR group (p < 0.05). Western blot results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the protein levels of Nrf2 and NQO1. Compared with the IUGR group, pigs in IUGR + CUR group showed significantly decreased the levels of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interferon gamma (IFNγ) (p < 0.05), and increased the interleukin-2 (IL-2) level (p < 0.05). Dietary supplementation with 200 mg/kg curcumin significantly reduced cysteinyl aspartate specific proteinase 3 (caspase3), BCL2-associated X protein (bax), B-cellCLL/lymphoma 2 (bcl2), and heat-shock protein 70 (hsp70) mRNA expression, and increased occludin (ocln) mRNA expression (p < 0.05). In conclusion, dietary supplementation with 200 mg/kg curcumin can alleviate jejunum damage in IUGR growing pigs, through Nrf2/Keap1 pathway.