白藜芦醇通过TGF-β信号通路对肠黏膜屏障功能的调控
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摘要
肠道健康水平对动物整体健康水平十分重要。作为机体抵御致病抗原入侵的防线,肠黏膜屏障的完整性极易受到损害。白藜芦醇是一种多酚类抗毒素,主要通过抗炎、抗纤维化、抗氧化等多种途径,对肠道黏膜屏障损伤及功能障碍发挥作用。转化生长因子-β(TGF-β)是一种多功能细胞因子,具有与白藜芦醇相似的功能。白藜芦醇可以通过对TGF-β/Smads信号通路的调控来影响肠道的健康。文章综述了白藜芦醇和TGF-β对肠黏膜屏障功能的作用以及白藜芦醇通过TGF-β信号通路对肠道健康的调控方式,为白藜芦醇在动物生产中的应用提供参考。
Intestinal health is very important for the overall health of animals. As the defense against invasion of pathogenic antigens, the integrity of intestinal mucosal barrier is vulnerable to be damaged. Resveratrol(Res), a polyphenolic phytoalexin, is effective in regulating immunity and protecting intestinal barrier through anti-inflammatory,anti-oxidative, anti-proliferative and other ways. Transforming growth factor-β(TGF-β) is one of the pleiotropic cytokines that also displays such properties as Res. Res can regulate intestinal health through the TGF-β/Smads signaling pathway. The effects of resveratrol and TGF-β on intestinal mucosal barrier function and the regulation of resveratrol through TGF-β signaling pathway on intestinal health were reviewed, so as to provide reference for the application of resveratrol in animal production.
Intestinal health is very important for the overall health of animals. As the defense against invasion of pathogenic antigens, the integrity of intestinal mucosal barrier is vulnerable to be damaged. Resveratrol(Res), a polyphenolic phytoalexin, is effective in regulating immunity and protecting intestinal barrier through anti-inflammatory,anti-oxidative, anti-proliferative and other ways. Transforming growth factor-β(TGF-β) is one of the pleiotropic cytokines that also displays such properties as Res. Res can regulate intestinal health through the TGF-β/Smads signaling pathway. The effects of resveratrol and TGF-β on intestinal mucosal barrier function and the regulation of resveratrol through TGF-β signaling pathway on intestinal health were reviewed, so as to provide reference for the application of resveratrol in animal production.
引文
[1] Cao S, Shen Z, Wang C, et al. Resveratrol improves intestinal barrier function, alleviates mitochondrial dysfunction and induces mitophagy in diquat challenged piglets[J]. Food&Funct., 2019, 10(1):344-354.
[2]黄进,张勇,于翠平,等.TGF-β/Smads信号通路在动物肠黏膜屏障改变中的作用[J].饲料研究,2013(7):20-22.
[3]陈代文,毛湘冰,余冰.猪抗病营养研究进展[J].动物营养学报,2014,26(10):2992-3002.
[4] De La Lastra C A, Villegas I. Resveratrol as an antioxidant and prooxidant agent:mechanisms and clinical implications[J]. Biochem. Soc. T.,2007, 35(5):1156-1160.
[5]曹宇,吴敏,刘龙涛,等.白藜芦醇对炎症反应microRNA调节作用[J].中国中西医结合杂志,2016,36(1):125-128.
[6]高润颖,蔡美琴.白藜芦醇对肠道保护作用的研究进展[J].上海交通大学学报(医学版),2016,36(2):302.
[7] Zhang C Y, Huang J, Kang X T. Resveratrol Attenuates LPS-induced Apoptosis via Inhibiting NF-κB Activity in Chicken Peripheral Lymphocyte Cultures[J]. Braz. J. Poultry Sci., 2018, 20(4):747-752.
[8] Al Azzaz J, Rieu A, Aires V, et al. Resveratrol-induced xenophagy promotes intracellular bacteria clearance in intestinal epithelial cells and macrophages[J]. Front Immuno., 2019, 9:3149.
[9] Yu Y, Li J, Pan J, et al. Resveratrol improves brain-gut axis by regulation of 5-HT-dependent signaling in the rat model of irritable bowel syndrome[J]. Front Cell Neurosci., 2019, 13:30.
[10] Dong W P, Li F F, Pan Z G, et al. Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury[J]. J. Surg. Res., 2013, 185(1):182-189.
[11] Alrafas H R, Busbee P B, Nagarkatti M, et al. Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells[J]. J. Leukoc. Biol., 2019 Mar 21.doi:10.1002/JLB.3A1218-476RR.[Epub ahead of print].
[12] Ye G, Chen G, Gao H, et al. Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages[J]. J. Cell Mol.Med., 2019 Apr 7. doi:10.1111/jcmm.14323[Epub ahead of print].
[13] Zhao W, Huang X, Han X, et al. Resveratrol suppresses gut-derived NLRP3 inflammasome partly through stabilizing mast cells in a rat model[J]. Mediators Inflamm., 2018, 2018:1-10.
[14]胡瑶莲,张恒志,陈代文,等.白藜芦醇对生长育肥猪抗氧化能力、空肠黏膜免疫及结肠菌群的影响[J].动物营养学报,2019,31(1):459-68.
[15] Gan Z, Wei W, Li Y, et al. Curcumin and resveratrol regulate intestinal bacteria and alleviate intestinal inflammation in weaned piglets[J].Molecules., 2019, 24(7):1220.
[16]黄超.白藜芦醇对氧化应激肉鸡肠道结构和抗氧化能力的影响[C]//中国畜牧兽医学会动物营养学分会.中国畜牧兽医学会动物营养学分会第十二次动物营养学术研讨会论文集.中国畜牧兽医学会动物营养学分会,2016.
[17]刘丽莉.白藜芦醇对乌骨鸡热应激损伤的修复机制研究[D].长沙:湖南农业大学,2014
[18] Mayangsari Y, Suzuki T. Resveratrol enhances intestinal barrier function by ameliorating barrier disruption in Caco-2 cell monolayers[J]. J. of Funct. Foods., 2018, 51:39-46.
[19] Buhrmann C, Yazdi M, Popper B, et al. Resveratrol Chemosensitizes TNF-β-induced survival of 5-FU-treated colorectal Cancer cells[J].Nutrients., 2018, 10(7):888.
[20] Garcia P, Schmiedlin-Ren P, Mathias J S, et al. Resveratrol causes cell cycle arrest, decreased collagen synthesis, and apoptosis in rat intestinal smooth muscle cells[J]. Am. J. Physiol. Gastrointest. Liver. Physiol.,2011, 302(3):326-335.
[21] Choi J H, Hwang Y P, Kim H G. Saponins from the roots of Platycodon grandiflorum suppresses TGFβ1-induced epithelial-mesenchymal transition via repression of PI3K/Akt, ERK1/2 and Smad2/3 pathway in human lung carcinoma A549 cells[J]. Nutr. Cancer., 2014, 66(1):140-151.
[22] Li X, Zhang L, Yin X, et al. Retinoic acid remodels extracellular matrix(ECM)of cultured human fetal palate mesenchymal cells(hFPMCs)through down-regulation of TGF-β/Smad signaling[J]. Toxicol Lett.,2014, 225(2):208-215.
[23] Mucida D, Park Y, Cheroutre H. From the diet to the nucleus:vitamin A and TGF-βjoin efforts at the mucosal interface of the intestine[J].Seminars in Immunology Academic Pres, 2009, 21(1):14-21.
[24] Jakowlew S B, Mathias A, Lillehoj H S. Transforming growth factorbeta isoforms in the developing chicken intestine and spleen:increase in transforming growth factor-beta 4 with coccidia infection[J]. Vet.Immunol. Immunop., 1997, 55(4):321-339.
[25] Song H, Song X, Xu L, et al. Changes of cytokines and IgG antibody in chickens vaccinated with DNA vaccines encoding Eimeria acervulina lactate dehydrogenase[J]. Vet. Parasitol., 2010, 173(3/4):219-227.
[26]张磊. TGF-β/Smads信号通路在雏鸡肠道损伤中的作用研究[D].郑州:河南工业大学,2016.
[27]黄进,殷海成,徐元红,等.鸡盲肠上皮细胞TGF-β信号通路与球虫感染浓度的关系研究[J].中国畜牧杂志,2018,54(6):118-121.
[28] Rahal K, Schmiedlin-Ren P, Adler J, et al. Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan-polysaccharide rat model of Crohn's disease[J]. Inflamm. Bowel. Dis., 2012, 18(4):613-623.
[29] Ji Q, Liu X, Han Z, et al. Resveratrol suppresses epithelial-tomesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression[J]. BMC Cancer., 2015, 15(1):97.
[30] Farooqi A, Khalid S, Ahmad A. Regulation of cell signaling pathways and miRNAs by resveratrol in different cancers[J]. Int. J. Mol. Sci., 2018,19(3):652.
[31]王师英,林江,邢立凯,等.白藜芦醇调控TGFβ1/Smad信号通路抑制胃癌MGC803细胞增殖机制探讨[J].现代肿瘤医学,2016,24(23):3713-3717.
[32] Tili E, Michaille J J, Alder H, et al. Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβsignaling pathway in SW480 cells[J]. Biochem. Pharmacol.,2010, 80(12):2057-2065.
[33]周玲芝,尹进.白藜芦醇酒剂对小鼠免疫功能影响的研究[J].湖南中医药大学学报,2009,29(1):41.
[2]黄进,张勇,于翠平,等.TGF-β/Smads信号通路在动物肠黏膜屏障改变中的作用[J].饲料研究,2013(7):20-22.
[3]陈代文,毛湘冰,余冰.猪抗病营养研究进展[J].动物营养学报,2014,26(10):2992-3002.
[4] De La Lastra C A, Villegas I. Resveratrol as an antioxidant and prooxidant agent:mechanisms and clinical implications[J]. Biochem. Soc. T.,2007, 35(5):1156-1160.
[5]曹宇,吴敏,刘龙涛,等.白藜芦醇对炎症反应microRNA调节作用[J].中国中西医结合杂志,2016,36(1):125-128.
[6]高润颖,蔡美琴.白藜芦醇对肠道保护作用的研究进展[J].上海交通大学学报(医学版),2016,36(2):302.
[7] Zhang C Y, Huang J, Kang X T. Resveratrol Attenuates LPS-induced Apoptosis via Inhibiting NF-κB Activity in Chicken Peripheral Lymphocyte Cultures[J]. Braz. J. Poultry Sci., 2018, 20(4):747-752.
[8] Al Azzaz J, Rieu A, Aires V, et al. Resveratrol-induced xenophagy promotes intracellular bacteria clearance in intestinal epithelial cells and macrophages[J]. Front Immuno., 2019, 9:3149.
[9] Yu Y, Li J, Pan J, et al. Resveratrol improves brain-gut axis by regulation of 5-HT-dependent signaling in the rat model of irritable bowel syndrome[J]. Front Cell Neurosci., 2019, 13:30.
[10] Dong W P, Li F F, Pan Z G, et al. Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury[J]. J. Surg. Res., 2013, 185(1):182-189.
[11] Alrafas H R, Busbee P B, Nagarkatti M, et al. Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells[J]. J. Leukoc. Biol., 2019 Mar 21.doi:10.1002/JLB.3A1218-476RR.[Epub ahead of print].
[12] Ye G, Chen G, Gao H, et al. Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages[J]. J. Cell Mol.Med., 2019 Apr 7. doi:10.1111/jcmm.14323[Epub ahead of print].
[13] Zhao W, Huang X, Han X, et al. Resveratrol suppresses gut-derived NLRP3 inflammasome partly through stabilizing mast cells in a rat model[J]. Mediators Inflamm., 2018, 2018:1-10.
[14]胡瑶莲,张恒志,陈代文,等.白藜芦醇对生长育肥猪抗氧化能力、空肠黏膜免疫及结肠菌群的影响[J].动物营养学报,2019,31(1):459-68.
[15] Gan Z, Wei W, Li Y, et al. Curcumin and resveratrol regulate intestinal bacteria and alleviate intestinal inflammation in weaned piglets[J].Molecules., 2019, 24(7):1220.
[16]黄超.白藜芦醇对氧化应激肉鸡肠道结构和抗氧化能力的影响[C]//中国畜牧兽医学会动物营养学分会.中国畜牧兽医学会动物营养学分会第十二次动物营养学术研讨会论文集.中国畜牧兽医学会动物营养学分会,2016.
[17]刘丽莉.白藜芦醇对乌骨鸡热应激损伤的修复机制研究[D].长沙:湖南农业大学,2014
[18] Mayangsari Y, Suzuki T. Resveratrol enhances intestinal barrier function by ameliorating barrier disruption in Caco-2 cell monolayers[J]. J. of Funct. Foods., 2018, 51:39-46.
[19] Buhrmann C, Yazdi M, Popper B, et al. Resveratrol Chemosensitizes TNF-β-induced survival of 5-FU-treated colorectal Cancer cells[J].Nutrients., 2018, 10(7):888.
[20] Garcia P, Schmiedlin-Ren P, Mathias J S, et al. Resveratrol causes cell cycle arrest, decreased collagen synthesis, and apoptosis in rat intestinal smooth muscle cells[J]. Am. J. Physiol. Gastrointest. Liver. Physiol.,2011, 302(3):326-335.
[21] Choi J H, Hwang Y P, Kim H G. Saponins from the roots of Platycodon grandiflorum suppresses TGFβ1-induced epithelial-mesenchymal transition via repression of PI3K/Akt, ERK1/2 and Smad2/3 pathway in human lung carcinoma A549 cells[J]. Nutr. Cancer., 2014, 66(1):140-151.
[22] Li X, Zhang L, Yin X, et al. Retinoic acid remodels extracellular matrix(ECM)of cultured human fetal palate mesenchymal cells(hFPMCs)through down-regulation of TGF-β/Smad signaling[J]. Toxicol Lett.,2014, 225(2):208-215.
[23] Mucida D, Park Y, Cheroutre H. From the diet to the nucleus:vitamin A and TGF-βjoin efforts at the mucosal interface of the intestine[J].Seminars in Immunology Academic Pres, 2009, 21(1):14-21.
[24] Jakowlew S B, Mathias A, Lillehoj H S. Transforming growth factorbeta isoforms in the developing chicken intestine and spleen:increase in transforming growth factor-beta 4 with coccidia infection[J]. Vet.Immunol. Immunop., 1997, 55(4):321-339.
[25] Song H, Song X, Xu L, et al. Changes of cytokines and IgG antibody in chickens vaccinated with DNA vaccines encoding Eimeria acervulina lactate dehydrogenase[J]. Vet. Parasitol., 2010, 173(3/4):219-227.
[26]张磊. TGF-β/Smads信号通路在雏鸡肠道损伤中的作用研究[D].郑州:河南工业大学,2016.
[27]黄进,殷海成,徐元红,等.鸡盲肠上皮细胞TGF-β信号通路与球虫感染浓度的关系研究[J].中国畜牧杂志,2018,54(6):118-121.
[28] Rahal K, Schmiedlin-Ren P, Adler J, et al. Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan-polysaccharide rat model of Crohn's disease[J]. Inflamm. Bowel. Dis., 2012, 18(4):613-623.
[29] Ji Q, Liu X, Han Z, et al. Resveratrol suppresses epithelial-tomesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression[J]. BMC Cancer., 2015, 15(1):97.
[30] Farooqi A, Khalid S, Ahmad A. Regulation of cell signaling pathways and miRNAs by resveratrol in different cancers[J]. Int. J. Mol. Sci., 2018,19(3):652.
[31]王师英,林江,邢立凯,等.白藜芦醇调控TGFβ1/Smad信号通路抑制胃癌MGC803细胞增殖机制探讨[J].现代肿瘤医学,2016,24(23):3713-3717.
[32] Tili E, Michaille J J, Alder H, et al. Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβsignaling pathway in SW480 cells[J]. Biochem. Pharmacol.,2010, 80(12):2057-2065.
[33]周玲芝,尹进.白藜芦醇酒剂对小鼠免疫功能影响的研究[J].湖南中医药大学学报,2009,29(1):41.