白藜芦醇及其衍生物对断奶仔猪生长性能、肝脏损伤及内质网应激的影响

Effects of resveratrol and its derivative on growth performance and hepatic damage and endoplasmic reticulum stress of weaned piglets

摘要

[目的]本试验旨在探索日粮添加白藜芦醇及其衍生物紫檀芪对断奶仔猪生长性能、肝脏损伤及内质网应激的影响。[方法]选用 300 头 21 日龄杜×长×大三元断奶仔猪,随机分为 5 个处理组,每组 6 个重复,每重复 10 头仔猪。对照组饲喂基础日粮,白藜芦醇组饲喂含有 250mg·kg^-1白藜芦醇的试验日粮,紫檀芪组分别饲喂含有 100、250 和 500mg·kg^-1紫檀芪的试验日粮。试验期为 21d,统计仔猪生长性能,并于试验结束时每重复随机选取 1 头仔猪屠宰,采集血液和肝脏样本用于生化指标检测。[结果]添加 250 和 500mg·kg^-1紫檀芪能够显著提高仔猪断奶后 3 周内饲料效率(P<0.05),且 250mg·kg^-1紫檀芪组平均日增重与对照组相比有升高趋势(P=0.067)。添加 250mg·kg^-1白藜芦醇降低了断奶仔猪肝脏细胞凋亡水平(P=0.098),而分别添加 250 和 500mg·kg^-1紫檀芪均显著减少断奶仔猪肝脏细胞凋亡比例(P<0.05)。与对照组相比,白藜芦醇组肝脏活化转录因子 6 和葡萄糖调节蛋白 78 表达水平显著下调(P<0.05),250 和 500mg·kg^-1紫檀芪组肝脏蛋白激酶 R 样内质网激酶、活化转录因子 6、葡萄糖调节蛋白 78 及 CCAAT 增强子结合蛋白同源蛋白等内质网应激相关基因转录水平均显著降低(P<0.05),而去乙酰化酶 1 活性明显升高(P<0.05)。添加 250mg·kg^-1紫檀芪显著提高断奶仔猪肝脏钙连接蛋白表达水平(P<0.05)。[结论]紫檀芪在提高断奶仔猪生长性能、减轻肝脏损伤及调节肝脏内质网应激方面较白藜芦醇效果更优,其添加量以 250mg·kg^-1为宜。

Abstract

[Objectives]The aim of this study was to investigate the effects of dietary supplementation with resveratrol and its derivative pterostilbene on growth performance, hepatic damage, and endoplasmic reticulum stress (ERS) in weaned piglets. [Methods]A total of 300 21-day-old weaned piglets Duroc × Landrace × Large White were randomly assigned to five treatment groups, with six replicates per group and ten piglets per replicate. The control group was fed a basal diet, while the resveratrol group was fed a diet supplemented with 250 mg·kg^-1 resveratrol. The pterostilbene groups were fed diets supplemented with 100, 250, and 500 mg·kg^-1 pterostilbene. The experiment lasted for 21 days, during which growth performance was recorded. At the end of the trial, one piglet from each replicate was randomly selected for slaughter and sampling. [Results]Supplementation with 250 and 500 mg·kg^-1 pterostilbene significantly improved feed efficiency in piglets during the 3-week post-weaning period (P<0.05), and the 250 mg·kg^-1 pterostilbene group showed a tendency to increase average daily gain compared with the control group (P=0.067). Supplementation with 250 mg·kg^-1 resveratrol partially reduced liver cell apoptosis in weaned piglets (P=0.098), whereas 250 and 500 mg·kg^-1 pterostilbene significantly decreased the levels of apoptotic liver cells (P<0.05). Compared with the control group, the resveratrol group exhibited significantly lower expression levels of activating transcription factor 6 (ATF6) and glucose-regulated protein 78 (GRP78) in the liver (P<0.05). The 250 and 500 mg·kg^-1 pterostilbene groups showed significantly reduced transcription levels of ERS-related genes, including protein kinase R-like ER kinase, ATF6, GRP78, and C/EBP homologous protein compared with the control group (P<0.05), while sirtuin 1 activity was significantly increased (P<0.05). Additionally, supplementation with 250 mg·kg^-1 pterostilbene significantly increased calnexin expression levels in the liver (P<0.05). [Conclusions]Pterostilbene was more effective than resveratrol in improving growth performance, alleviating hepatic damage, and regulating ER stress in weaned piglets, with an optimal level of 250 mg·kg^-1.

关键词

断奶仔猪 / 肝脏损伤 / 内质网应激 / 白藜芦醇 / 紫檀芪

Key words

weaned piglet / hepatic damage / endoplasmic reticulum stress / resveratrol / pterostilbene

参考文献

[1] Tang XP, Xiong KN, Fang RJ, et al. Weaning stress and intestinal health of piglets: a review[J]. Frontiers in Immunology, 2022, 13: 1042778.

[2] Yu LH, Li HM, Peng Z, et al. Early weaning affects liver antioxidant function in piglets[J]. Animals, 2021, 11(9): 2679.

[3] 张相雷, 金灵红, 杨金玉, 等. 湿法膨化和发酵豆粕对断奶仔猪生长性能、免疫功能及氨基酸消化率的影响[J]. 南京农业大学学报, 2024, 47: 113-122. DOI: 10.7685/jnau.202206036.

[4] Zhang XL, Jin LH, Yang JY, et al. Effects of wet extruded and fermented soybean meal on growth performance, immune function and amino acid digestibility in weaned piglets[J]. Journal of Nanjing Agricultural University, 2024, 47(1): 113-122 (in Chinese with English abstract).

[5] 邵云, 胡琴, 王春梅, 等. 合生元对断奶仔猪生长性能、血清抗氧化能力、生化指标和粪便微生物的影响[J]. 畜牧与兽医, 2024, 56: 23-27.

[6] Shao Y, Hu Q, Wang CM, et al. Effects of synbiotic supplementation on growth performance, serum antioxidant capacity, biochemical indices and fecal microbiota in weaned piglets[J]. Animal Husbandry & Veterinary Medicine, 2024, 56(5): 23-27 (in Chinese with English abstract).

[7] Ajoolabady A, Kaplowitz N, Lebeaupin C, et al. Endoplasmic reticulum stress in liver diseases[J]. Hepatology, 2023, 77(2): 619-639.

[8] 赵丽. 仔猪早期断奶应激诱导肝脏发生内质网应激及其营养调节的研究[D]. 武汉: 华中农业大学, 2014.

[9] Zhao L. Study on endoplasmic reticulum stress induced by early weaning stress in piglets and its nutritional regulation[D]. Wuhan: Huazhong Agricultural University, 2014 (in Chinese with English abstract).

[10] Bhattarai KR, Riaz TA, Kim HR, et al. The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling[J]. Experimental & Molecular Medicine, 2021, 53(2): 151-167.

[11] Lee JM, Hong SW, Park SE, et al. Exendin-4 attenuates endoplasmic reticulum stress through a SIRT1-dependent mechanism[J]. Cell Stress & Chaperones, 2014, 19(5): 649-656.

[12] Wang FQ, Yao SL, Xia HF. SIRT1 is a key regulatory target for the treatment of the endoplasmic reticulum stress-related organ damage[J]. Biomedicine & Pharmacotherapy, 2020, 130: 110601.

[13] Jung TW, Lee KT, Lee MW, et al. SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150[J]. Biochemical and Biophysical Research Communications, 2012, 422(2): 229-232.

[14] Zhang LX, Li CX, Kakar MU, et al. Resveratrol (RV): a pharmacological review and call for further research[J]. Biomedicine & Pharmacotherapy, 2021, 143: 112164.

[15] Tsai HY, Ho CT, Chen YK. Biological actions and molecular effects of resveratrol, pterostilbene, and 3'-hydroxypterostilbene[J]. Journal of Food and Drug Analysis, 2017, 25(1): 134-147.

[16] Guo Y, Zhang L, Li F, et al. Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes[J]. European Journal of Pharmacology, 2016, 776: 26-33.

[17] Chang J, Rimando A, Pallas M, et al. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease[J]. Neurobiology of Aging, 2012, 33(9): 2062-2071.

[18] Mccormack D, Mcfadden D. A review of pterostilbene antioxidant activity and disease modification[J]. Oxidative Medicine and Cellular Longevity, 2013, 2013: 575482.

[19] Lin HS, Yue BD, Ho PC. Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study[J]. Biomedical Chromatography, 2009, 23(12): 1308-1315.

[20] Zhang H, Chen YN, Chen YP, et al. Comparison of the effects of resveratrol and its derivative pterostilbene on hepatic oxidative stress and mitochondrial dysfunction in piglets challenged with diquat[J]. Food & Function, 2020, 11(5): 4202-4215.

[21] Zhang H, Chen YN, Chen YP, et al. Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets[J]. Journal of Animal Science and Biotechnology, 2020, 11(1): 52.

[22] Gan ZD, Wei WY, Wu JM, et al. Resveratrol and curcumin improve intestinal mucosal integrity and decrease m⁶A RNA methylation in the intestine of weaning piglets [J]. ACS Omega, 2019, 4(17): 17438-17446.

[23] Zhang C, Luo JQ, Yu B, et al. Dietary resveratrol supplementation improves meat quality of finishing pigs through changing muscle fiber characteristics and antioxidative status[J]. Meat Science, 2015, 102: 15-21.

[24] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2^-ΔΔCt Method [J]. Methods, 2001, 25(4): 402-408.

[25] Xun WJ, Fu QY, Hou GY, et al. Protective effects of dietary resveratrol supplementation against oxidative stress in diquat-challenged piglets[J]. Italian Journal of Animal Science, 2020, 19(1): 1523-1532.

[26] Cao ST, Shen ZJ, Wang CC, et al. Resveratrol improves intestinal barrier function, alleviates mitochondrial dysfunction and induces mitophagy in diquat challenged piglets¹ [J]. Food & Function, 2019, 10(1): 344-354.

[27] Zhang H, Li Y, Su WP, et al. Resveratrol attenuates mitochondrial dysfunction in the liver of intrauterine growth retarded suckling piglets by improving mitochondrial biogenesis and redox status[J]. Molecular Nutrition & Food Research, 2017, 61(5): 1600653.

[28] Hong QH, Li X, Lin Q, et al. Resveratrol improves intestinal morphology and anti-oxidation ability in deoxynivalenol-challenged piglets[J]. Animals, 2022, 12(3): 311.

[29] Meng QW, Sun SS, Luo Z, et al. Maternal dietary resveratrol alleviates weaning-associated diarrhea and intestinal inflammation in pig offspring by changing intestinal gene expression and microbiota[J]. Food & Function, 2019, 10(9): 5626-5643.

[30] Yeo SCM, Fenwick PS, Barnes PJ, et al. Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism[J]. British Journal of Pharmacology, 2017, 174(13): 2043-2059.

[31] Dellinger RW, Gomez Garcia AM, Meyskens FL. Differences in the glucuronidation of resveratrol and pterostilbene: altered enzyme specificity and potential gender differences[J]. Drug Metabolism and Pharmacokinetics, 2014, 29(2): 112-119.

[32] Chiou YS, Tsai ML, Wang YJ, et al. Pterostilbene inhibits colonic aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice[J]. Journal of Agricultural and Food Chemistry, 2010, 58(15): 8833-8841.

[33] Choo QY, Yeo SCM, Ho PC, et al. Pterostilbene surpassed resveratrol for anti-inflammatory application: potency consideration and pharmacokinetics perspective[J]. Journal of Functional Foods, 2014, 11: 352-362.

[34] Zhang H, Chen YN, Li Y, et al. Protective effects of pterostilbene against hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum stress in weanling piglets[J]. Journal of Animal Science, 2020, 98(10): skaa328.

[35] Ikeda T, Yanaga K, Kishikawa K, et al. Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats[J]. Hepatology, 1992, 16(2): 454-461.

[36] Asadi M, Taghizadeh S, Kaviani E, et al. Caspase-3: structure, function, and biotechnological aspects[J]. Biotechnology and Applied Biochemistry, 2022, 69(4): 1633-1645.

[37] An JH, Zhang X, Jia KQ, et al. Trichostatin A increases BDNF protein expression by improving XBP-1s/ATF6/GRP78 axis in Schwann cells of diabetic peripheral neuropathy[J]. Biomedicine & Pharmacotherapy, 2021, 133: 111062.

[38] Grechowa I, Horke S, Wallrath A, et al. Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response[J]. FASEB Journal, 2017, 31(9): 3868-3881.

[39] Hu H, Tian MX, Ding C, et al. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection[J]. Frontiers in Immunology, 2019, 9: 3083.

[40] Marciniak SJ, Yun CY, Oyadomari S, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum[J]. Genes & Development, 2004, 18(24): 3066-3077.

基金资助

国家自然科学基金项目(32272917)

江苏省农业科技自主创新资金项目(CX(22)2019)

中央财政林业改革发展(林业科技推广示范项目)(鲁〔2023〕TG-07号)