动物营养学报 >

2023 , Vol. 35 >Issue 5: 2729 - 2737

DOI: https://doi.org/10.12418/CJAN2023.255

综述

丁酸钠调控肠道屏障的作用机制及其在肉鸡养殖中的应用

  • 王宗伟 , 1, 2 ,
  • 庄佳荣 3 ,
  • 李洪涛 3 ,
  • 赵旭 , 1, *
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  • 1 临沂大学农林科学学院,临沂 276000
  • 2 寿光市政务服务中心,寿光 262700
  • 3 临沂布恩生物科技有限公司,临沂 276036
*赵 旭,副教授,E-mail:

王宗伟(1982—),男,山东寿光人,高级畜牧师、执业兽医师,硕士,主要从事动物营养与畜禽疾病的研究。E-mail:

Copy editor: 田艳明

收稿日期: 2022-11-03

  网络出版日期: 2023-05-11

基金资助

山东省重点研发计划(重大科技创新工程)项目(2019JZZY020609)

临沂大学高层次人才科研启动项目(LYDX2019BS036)

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Mechanism of Sodium Butyrate Regulating Intestinal Barrier and Its Application in Broiler Breeding

  • WANG Zongwei , 1, 2 ,
  • ZHUANG Jiarong 3 ,
  • LI Hongtao 3 ,
  • ZHAO Xu , 1, *
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  • 1 College of Agriculture and Forestry Science, Linyi University, Linyi 276000, China
  • 2 Shouguang Government Service Center, Shouguang 262700, China
  • 3 Linyi Backbone Biotechnology Co., Ltd., Linyi 276036, China
*associate professor, E-mail:

Received date: 2022-11-03

  Online published: 2023-05-11

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摘要

肠道屏障不仅是肠道选择性消化吸收营养物质的结构基础,也是肠道不断接受外界刺激的保护性屏障。丁酸钠能够通过调控组蛋白乙酰化、G蛋白偶联受体等多条途径,保持肠道黏膜上皮完整,增强肠道免疫功能,降低肠道炎症水平和维持肠道菌群平衡等,发挥抗病促生长的作用。本文综述了丁酸钠调控肠道屏障的作用机制及其在肉鸡养殖中的应用,以期为丁酸钠在肉鸡营养上发挥替抗作用提供参考。

关键词： 丁酸钠; 肠道屏障; 肉鸡; 炎症; 促生长

本文引用格式

王宗伟 , 庄佳荣 , 李洪涛 , 赵旭 . 丁酸钠调控肠道屏障的作用机制及其在肉鸡养殖中的应用[J]. 动物营养学报, 2023 , 35(5) : 2729 -2737 . DOI: 10.12418/CJAN2023.255

Abstract

The intestinal barrier is not only a structural basis for selective digestion and absorption of nutrients, but also a protective barrier for the intestinal tract to continuously receive external stimuli. Sodium butyrate can maintain the integrity of intestinal mucosal epithelium, enhance intestinal immune function, reduce intestinal inflammation and maintain intestinal microbiota balance by regulating histone acetylation, G protein-coupled receptor and other pathways, so as to play the role of disease resistance and growth promotion. This review summarized the mechanism of sodium butyrate regulating intestinal barrier and its application in broiler breeding, in order to provide references for sodium butyrate to replace antibiotics in broiler nutrition.

Key words： sodium butyrate; intestinal barrier; broilers; inflammation; growth promotion

随着饲料配方、遗传育种和饲养管理技术的进步,肉鸡的生长速度和饲料利用率已大幅提高。在生产实践中,42日龄爱拔益加(AA)和罗斯308肉鸡体重能达到3 kg,料重比低于1.4。不过,肉鸡由于生长速度快,肠道功能发育不完善,细菌等微生物容易侵入肠道屏障,引发肠道乃至全身感染。在饲料禁抗背景下,保障肉鸡肠道健康和快速、高效消化吸收营养物质的能力具有极大的挑战性。研究表明,丁酸钠能够迅速通过选择性增强染色质核小体中组蛋白乙酰化[1],使核小体结构松散,从而调控功能蛋白和mRNA的表达[2];丁酸钠还能够通过调节G蛋白偶联受体(G protein-coupled receptor,GPR)、Toll样受体(Toll-like receptor,TLR)等多条炎症通路,控制炎症水平[3-4]。适量的丁酸钠具有促进肠道发育,增强肠道免疫功能和调节肠道菌群平衡等多种作用[5⇓-7]。本文综述了丁酸钠调控肠道屏障的作用机制及其在肉鸡养殖中的应用。

1 丁酸钠的物理特性、添加形式及吸收方式

丁酸钠又称正丁酸钠,分子式为C4H7O2Na,相对分子质量为110.09,呈似绒毛状的白色或类白色可吸湿性粉末,具有特殊的奶酪酸败样气味,易溶于水,水溶液呈碱性。作为饲料添加剂使用的丁酸钠,有结晶粉末和包被2种形式,由于丁酸钠结晶粉末存在易吸湿结块,有挥发性和脂臭味,以及不易在后部肠道发挥有益作用[8]等缺点,包被丁酸钠在肉鸡饲料中使用较广。经测算,非解离状态的丁酸钠在肉鸡嗉囊、腺胃和肌胃的比例分别为96.9%、1.3%和10.1%,在十二指肠、空肠、回肠和盲肠的比例分别为98.6%、98.3%、99.0%和99.5%[9⇓-11]。此外,非解离状态的丁酸钠是脂溶性的,以分子形式通过被动吸收快速进入胃肠道上皮细胞[9];而解离状态的丁酸根离子则主要由单羧酸转运蛋白(monocarboxylate transporter)通过主动运输进入胃肠道上皮细胞[12]。

2 丁酸钠调控肠道屏障的作用机制

肠道屏障是指肠道防止肠腔内有害物质透过肠黏膜吸收进入畜禽体内的结构和功能的总和,包括机械屏障、化学屏障、免疫屏障和微生物屏障[13]。丁酸钠通过调控组蛋白乙酰化、GPR等多条途径,保持肠道黏膜上皮完整,增强肠道免疫功能,降低肠道炎症水平和维持肠道菌群平衡等。

2.1 丁酸钠对肠道机械屏障的影响

肠道机械屏障主要是由柱状上皮细胞和细胞间的紧密连接——密封蛋白(claudin,Cldn)、闭合蛋白(occludin,Ocln)和闭锁小带蛋白(zonula occlaudin,ZO)组成[14]。丁酸钠对肠道机械屏障的影响表现在以下2个方面:1)细胞增殖。丁酸钠是大鼠结肠细胞的首选能量来源[15],能够显著促进无短链脂肪酸供应大鼠结肠黏膜的生长[16]。丁酸钠还能通过胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)信号通路间接促进羔羊瘤胃上皮细胞增殖[17]。2)紧密连接。丁酸钠通过激活细胞膜表面受体GPR109A,显著上调小鼠结肠组织Cldn1、Ocln和ZO1 mRNA的表达[3];通过单磷酸腺苷活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)/线粒体自噬途径显著提高过氧化氢(H2O2)诱导的猪小肠上皮细胞IPEC-J2中Cldn1、Ocln和ZO1的表达,缓解Cldn1分布紊乱[18]。

2.2 丁酸钠对肠道化学屏障的影响

肠道化学屏障主要包括覆盖在肠上皮表面起保护和润滑作用以黏蛋白(mucin,MUC)为主的黏液、消化液等。首先,丁酸钠显著增加肉鸡十二指肠、空肠和回肠分泌MUC的杯状细胞数量[19];通过激活细胞膜表面受体GPR109A,上调肠道最重要的黏蛋白——MUC2的表达[3]。其次,丁酸钠能够显著提高肉鸡回肠α-淀粉酶、脂肪酶和胰蛋白酶的活性[5]。再次,丁酸钠通过调节肠道菌群来增强法尼醇X受体/成纤维细胞生长因子-15/小异源二聚体伙伴(Farnesoid X receptor/fibroblast growth factor-15/small heterodimer partner,FXR/FGF-15/SHP)信号通路,抑制胆汁酸的合成[20]。

2.3 丁酸钠对肠道免疫屏障的影响

肠道免疫屏障主要由肠上皮细胞、肠内淋巴细胞和分泌型免疫球蛋白A(sIgA)等抗菌物质和淋巴组织等组成。丁酸钠主要通过抑制组蛋白去乙酰化酶(histone deacetylase,HDAC)、激活GPR信号通路等途径,增强肠道免疫和抗氧化功能,降低炎症水平。

2.3.1 增强肠道免疫功能

无病原微生物刺激时,丁酸钠通过促进树突状细胞定向迁移到肠道组织和宿主防御肽(host defense peptides,HDPs)的分泌,增强肠道的免疫功能。具体表现在以下2个方面:1)丁酸钠能够显著降低维甲酸诱导的树突状细胞中黏附分子整合素CD11c的表达,但显著提高肠道归巢受体α4β7和黏附分子整合素CD103的表达[21]。2)丁酸钠通过激活IPEC-J2细胞TLR2/核因子-κB(nuclear factor-κB,NF-κB)和表皮生长因子受体(epidermal growth factor receptor,EGFR)信号通路,上调β-防御素3(β-defensin 3,pBD3)和猪附睾蛋白2剪接变异C(porcine epididymis protein 2 splicing variant C,pEP2C)mRNA的表达[22];丁酸钠通过激活肠道上皮细胞GPR43/哺乳动物雷帕霉素靶蛋白(mammalian target protein of rapamycin,mTOR)和信号传导子及转录激活子3(signal transducer and activator of transcription 3,STAT3)信号通路,增强抗菌蛋白RegⅢγ和β-防御素的表达[23]。此外,丁酸钠还诱导鸡巨噬细胞HD11、鸡盲肠组织中禽β-防御素9(AvBD9)等HDPs基因的表达[24]。
有病原微生物刺激时,丁酸钠通过改变巨噬细胞的细胞结构,增加杀菌蛋白和HDPs的表达,促进肠道sIgA的分泌,增强肠道的免疫功能。具体表现在以下3个方面:1)丁酸钠通过减少鸡巨噬细胞中介导肌动蛋白细胞骨架重排的蛋白表达,以及影响细胞内肠炎沙门氏菌生长和复制的因素,降低感染引起的细胞骨架重排和细菌吞噬作用;还能增加被感染鸡巨噬细胞中与杀灭细菌有关的蛋白表达[6]。2)丁酸钠通过激活小鼠肠道上皮细胞GPR109A信号通路,上调多聚免疫球蛋白受体(polymeric immunoglobulin receptor,pIgR)基因的表达,促进肠道sIgA的分泌,从而抑制产肠毒素大肠杆菌的定植和迁移[25]。3)丁酸钠通过调控NOD样模式识别受体2(NOD-like receptor 2,NOD2)/半胱氨酸天冬氨酸蛋白酶-12(Caspase-12)信号通路,上调呕吐毒素诱导的IPEC-J2细胞pBD3和pEP2C mRNA的表达[26];通过抑制HDAC,上调猪巨噬细胞β-防御素2(β-defensin 2,pBD2)、pBD3 mRNA的表达[27]。

2.3.2 缓解肠道炎症

丁酸钠可通过调控不同种类免疫细胞的增殖和功能以及多条炎症信号通路来缓解炎症。丁酸钠能够显著抑制黏膜源树突状细胞诱导的CD4+ T细胞的增殖[21];减弱鼠伤寒沙门氏菌脂多糖诱导的鸡巨噬细胞(HTC细胞)的吞噬作用[28-29];通过增强组蛋白H3赖氨酸9(histone H3 at lysine 9,H3K9)信号传导子及转录激活子6(signal transducer and activator of transcription 6,STAT6)信号通路,促进白细胞介素-4(IL-4)诱导的M2巨噬细胞极化,显著增加精氨酸酶-1(arginase-1)的表达[30]。丁酸钠显著上调重症胰腺炎大鼠回肠、结肠中GPR109A、调节性T细胞(regulatory T-cell,Treg细胞)标志物——叉头/翼螺旋转录因子P3(Forkhead/winged helix transcription factor P3,FoxP3)mRNA的表达,极显著提高CD4+CD25+Foxp3+Treg细胞比例[7];此外,丁酸钠能够通过HDAC/p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38 MAPK)信号通路诱导小鼠脾脏B细胞分化为能够分泌白细胞介素-10(IL-10)的调节性B细胞[31],但丁酸钠是否会诱导肠系膜淋巴结中的B细胞分化有待进一步研究。丁酸钠通过调控GPR41[32]、GPR109A[3]、高迁移率族蛋白B1(high-mobility group box-1,HMGB1)[33]、c-Jun氨基末端蛋白激酶(c-Jun N-terminal kinase,JNK)[34]、过氧化物酶增殖物激活受体γ(PPARγ)[35]、核苷酸结合寡聚化结构域样受体家族含pyrin结构域蛋白3(nucleotide-binding oligomerization domain-like receptor family,pyrin domain-containing protein 3,NLRP3)[36]、转录因子芳基烃受体AhR[37]多条信号通路,上调抗炎因子——IL-10的表达,下调促炎因子——白细胞介素-1β(IL-1β)等的表达,缓解炎症。

2.3.3 提高肠道抗氧化性能

丁酸钠通过激活H2O2诱导的IPEC-J2细胞中AMPK/线粒体自噬途径,显著增强超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的活性,显著降低丙二醛(malondialdehyde,MDA)的含量,减轻线粒体细胞色素C(cytochrome C)的释放,缓解氧化应激和线粒体功能障碍[18]。

2.4 丁酸钠对肠道微生物屏障的影响

肠道微生物屏障主要包括益生菌在肠黏膜上皮定植形成的菌膜屏障,肠道内的菌群与机体形成的微生态平衡系统。体外试验表明,丁酸钠能够影响副溶血性弧菌菌体正常的代谢和功能[38],抑制3种血清型沙门氏菌的生长[39]。丁酸钠能够提高肉鸡盲肠内拟杆菌等有益菌的数量,有效缓解二硫代氨基甲酸盐类农药引起的肠道菌群紊乱[40];减少葡聚糖硫酸钠诱导的肠炎肉仔鸡盲肠中肠杆菌科的相对丰度,增加乳杆菌科的相对丰度[41]。

3 丁酸钠在肉鸡养殖中的应用

丁酸钠在提高肉鸡(尤其是白羽肉鸡)生长速度和营养物质利用率、缓解肠道炎症等方面,有较为显著的作用。肉鸡饲粮中分别添加1.0~1.5 g/kg丁酸钠、0.5~1.0 g/kg包被丁酸钠(丁酸钠含量30%~90%),抗病、促生长效果较好;当与精油或其他添加剂合用时,效果更显著。但丁酸钠能诱导马立克氏病毒活化[42],需要在生产中多加注意。

3.1 促生长和提高营养物质利用率

3.1.1 促生长

丁酸钠能够促进肉鸡肠道生长,调控肠道菌群平衡,提高肉鸡的生长速度和健康水平,有较好的替抗效果。Lan等[43]发现,随着1~21日龄AA肉鸡(公母各占1/2)饲粮中包被丁酸钠(丁酸钠含量54%)添加量的增加(0.3~1.2 g/kg),21日龄肉鸡小肠的相对重量和相对长度、盲肠的相对长度呈线性显著增加。Zhao等[5]在1~42日龄雄性AA肉仔鸡饲粮中分别添加抗生素(恩拉霉素8 mg/kg、金霉素0.1 g/kg)、包被丁酸钠(丁酸钠含量54%)1 g/kg,结果发现,与空白对照组相比,两者均可显著提高肉鸡的增重和饲料转化率,两者间差异不显著。Wan等[44]在Zhao等[5]试验的基础上继续研究发现,与抗生素组相比,包被丁酸钠组肉鸡肠道微生物中拟杆菌门的相对丰度显著升高,放线菌门的相对丰度显著降低;盲肠内容物中总短链脂肪酸水平显著升高。Mátis等[45]分别在1~42日龄罗斯308肉鸡饲粮中添加1.5 g/kg丁酸钠、2 g/kg包被丁酸钠(丁酸钠含量30%)、1.5 g/kg包被丁酸钠(丁酸钠含量40%)、1 g/kg包被丁酸钠(丁酸钠含量90%),结果发现,3个不同含量的包被丁酸钠组肉鸡42日龄体重均极显著高于空白对照组,其中1 g/kg包被丁酸钠组(丁酸钠含量90%)体重最高。Liu等[46]研究发现,丁酸钠比丁酸梭菌能更有效地促进1~42日龄科宝500肉鸡的生长和肠道发育,而丁酸梭菌在促进肠道紧密连接蛋白表达和抗炎反应方面优于丁酸钠。

3.1.2 提高营养物质利用率

丁酸钠能够提高肉鸡的营养物质利用率,缓解饲粮营养水平降低对肉鸡生长性能的影响。Liu等[47]在1~42日龄雄性科宝肉鸡饲粮中添加0.5~1.0 g/kg包被丁酸钠(丁酸钠含量30%)能够极显著提高42日龄肉鸡的回肠能量消化率。Moquet等[48]在1~21日龄雄性罗斯308肉鸡饲粮中添加0.421 g/kg包被丁酸钠(丁酸钠含量30%)能够显著提高饲料转化率,并有提高蛋氨酸等16种氨基酸回肠表观消化率的趋势。Bortoluzzi等[49]在1~28日龄雄性罗斯308肉仔鸡饲粮中添加1 g/kg包被丁酸钠(丁酸钠含量70%)能够显著逆转因饲粮(1~14日龄,代谢能12.77 MJ/kg、粗蛋白质22.17%;15~28日龄,代谢能13.19 MJ/kg,粗蛋白质20.78%)营养水平降低(代谢能降低0.25 MJ/kg,氨基酸降低2.3%)而导致的体增重下降。

3.2 缓解肠道炎症

3.2.1 坏死性肠炎

肉鸡在20~40日龄容易发生坏死性肠炎,其中球虫、产气荚膜梭菌和环境应激等是坏死性肠炎的重要诱因,丁酸钠与其他添加物联合使用可以起到较好的防治坏死性肠炎的效果。1)单独使用。Zhou等[50]在7~19日龄雄性罗曼肉鸡(14日龄柔嫩艾美尔球虫攻毒)饲粮中添加0.75 g/kg包膜丁酸钠(丁酸钠含量30%)能够显著抑制球虫引起的盲肠厚壁菌门丰度的增加和拟杆菌门丰度的降低,平衡盲肠菌群紊乱。Liu等[51]分别在1~21日龄科宝雄性肉仔鸡饲粮中添加0.5 g/kg包被丁酸钠(丁酸钠含量30%,过胃后释放时间2 h)、0.5 g/kg包被丁酸钠(丁酸钠含量30%,过胃后释放时间3~4 h),模拟坏死性肠炎感染(14日龄巨型艾美尔球虫、19~21日龄产气荚膜梭菌攻毒),结果发现,与对照组相比,过胃后释放时间2 h的包被丁酸钠能够显著提高1~21日龄肉鸡的增重和存活率(96.43% vs. 85.71%),显著降低21日龄肠道病变评分,但过胃后释放时间3~4 h的包被丁酸钠在提高肉鸡增重和存活率方面效果不明显。2)联合使用。Jerzsele等[52]在1~25日龄肉仔鸡饲粮中添加1.5 g/kg含有丁酸钠和精油(姜精油、香芹酚)的组合物,模拟坏死性肠炎临床特征(18~21日龄产气荚膜梭菌、19日龄球虫减毒活疫苗攻毒),结果发现,该组合物能够显著提高17~25日龄增重,极显著提高25日龄空肠绒毛高度和绒毛高度与隐窝深度比值,并显著降低25日龄小肠总病理和各组织病理评分。Yang等[53]研究表明,1 g/kg丁酸钠、10 mg/kg含有毛喉素的植物提取物和10 g/kg乳糖组合可显著逆转14~18日龄雄性科宝肉仔鸡坏死性肠炎合并感染(11日龄巨型艾美耳球虫、14~16日龄产气荚膜梭菌攻毒)引起的生长抑制,极显著提高14~18日龄肉仔鸡的存活率(94% vs. 39%),极显著降低18日龄空肠损伤评分和产气荚膜梭菌滴度,显著降低粪便中的球虫卵数量。

3.2.2 其他

丁酸钠能够降低肉鸡肠道和肝脏的沙门氏菌感染;缓解大肠杆菌刺激引起的肉鸡炎症,提高机体的抗氧化性能。Fernández-Rubio等[54]在1~42日龄罗斯肉鸡饲粮中分别添加0.92 g/kg丁酸钠、1.31 g/kg部分包被丁酸钠(丁酸钠含量70%,其中30%丁酸钠包被处理,40%丁酸钠不包被),5日龄接种肠炎沙门氏菌,结果发现,在27日龄以前,这2种添加方式均能显著降低肠炎沙门氏菌的感染;其中部分包被丁酸钠在感染后期效果更好,能够显著减少42日龄肉鸡嗉囊和盲肠,甚至肝脏的感染。Sunkara等[24]在5~11日龄雄性康沃尔肉仔鸡(7日龄噬菌体13a型肠炎沙门氏菌攻毒)饲粮中添加1 g/kg丁酸钠能够显著降低盲肠的细菌滴度。Zhang等[55]在1~42日龄爱拔益加(AA)肉鸡饲粮中添加1 g/kg丁酸钠,16、18、20日龄进行大肠杆菌脂多糖攻毒,结果发现,丁酸钠能够显著增强21日龄血清SOD和21、42日龄血清过氧化氢酶(catalase,CAT)活性,显著降低42日龄血清白细胞介素-6(IL-6)含量。

3.3 抗应激

丁酸钠能够缓解高温高湿、高密度饲养等应激因素引起的肉鸡抗氧化性能和肌肉品质降低。Lan等[56]研究发现,在高温高湿(32.53 ℃、相对湿度73.77%)环境下,随着包被丁酸钠(丁酸钠含量54%)添加量的增加(0.3~1.2 g/kg),1~35日龄雌性AA肉鸡肝脏SOD、CAT活性呈线性显著提高,肝脏MDA含量呈线性显著降低。Wu等[57]在21~42日龄科宝肉鸡饲粮中添加0.5 g/kg丁酸钠和0.05 g/kg烟酰胺,结果发现,丁酸钠和烟酰胺联合应用能够通过增强胸肌线粒体功能和抗氧化能力、抑制炎症反应和糖酵解、促进肌肉发育和透明质酸合成等方式显著缓解高饲养密度(18 vs. 14 只/m2)导致的胸肌品质(滴水损失率、蒸煮损失率和pH下降速率)降低。Zhang等[58]在1~42日龄AA肉鸡饲粮中添加0.4 g/kg包被丁酸钠(丁酸钠含量30%)能够显著降低肉鸡急性屠宰前应激(皮质激素刺激)造成的体重损失,显著提高胸肌CAT活性,极显著降低胸肌MDA含量。

3.4 增强免疫功能

丁酸钠能够提高肉鸡的免疫器官指数,增强细胞免疫和体液免疫,缓解有害菌对免疫器官和肠道的损伤。Sikandar等[59]在1~35日龄M77哈伯德肉鸡饲粮中添加1.0 g/kg 包被丁酸钠(丁酸钠含量30%),结果发现,包被丁酸钠组35日龄肉鸡细胞免疫(植物血凝素-p介导)、体液免疫(血清中新城疫病疫苗和羊红细胞抗体滴度)反应显著高于0.1 g/kg杆菌肽锌组和对照组。Lan等[43]研究发现,随着包被丁酸钠(丁酸钠含量54%)添加量的增加(0.3~1.2 g/kg),AA肉鸡(公母各占1/2)胸腺和脾脏的相对重量呈线性显著增加。Luo等[19]在1~42日龄罗斯308肉鸡饲粮中添加0.4 g/kg包被丁酸钠(丁酸钠含量30%),结果发现,包被丁酸钠能够显著提高42日龄肉鸡血浆中髓过氧化物酶(myeloperoxidase,MPO)活性及血清中免疫球蛋白G(IgG)和免疫球蛋白M(IgM)含量。Eshak等[60]在1~5周龄雄性AA肉鸡3阶段饲粮中分别添加1、0.5和0.25 g/kg包被丁酸钠(丁酸钠含量30%),14~17日龄产气荚膜梭菌攻毒,结果发现,包被丁酸钠能够显著下调5周龄肉鸡法氏囊中免疫蛋白编码基因——α-毒素(α-toxin)和甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GPD)的表达,减少肠道组织DNA的碎片化。

3.5 调节脂肪分布

丁酸钠能够调控肉鸡不同组织中的脂肪沉积。Zhao等[61]在诱导鸡原代前脂肪细胞分化为成熟脂肪细胞的过程中添加丁酸钠,结果发现,较低浓度(0.01 mmol/L)的丁酸钠能够显著下调游离脂肪酸受体(free fatty acid receptor,FFAR)介导的脂肪生成基因——脂肪酸合成酶(fatty acid synthase,FAS)、脂肪酸结合蛋白4(fatty acid binding protein 4,FABP4)等mRNA的表达,减少脂肪积累;较高浓度(1 mmol/L)的丁酸钠能够抑制HDAC活性,减少脂肪细胞的数量;动物试验进一步发现,饲粮中添加1 g/kg包被丁酸钠(丁酸钠含量70%)能够抑制1~42日龄雄性AA肉仔鸡肝脏和腹部的脂肪沉积。Mátis等[62]给20~24日龄罗斯308肉鸡每天投喂0.25 g/kg BW丁酸钠,连续4 d,结果发现,丁酸钠极显著抑制肉鸡肝脏、皮下和腹部脂肪组织胰岛素受体β亚基(insulin receptor β subunit,IRβ)的表达,但显著促进骨骼肌——腓肠肌IRβ的表达。Mátis等[45]在1~42日龄雄性罗斯308肉鸡低蛋白质饲粮(1~10日龄、11~25日龄和26~42日龄,粗蛋白质22.69% vs. 19.07%、21.36% vs. 18.01%、19.08% vs. 16.03%)中添加1.5 g/kg丁酸钠,结果发现,与正常蛋白质饲粮组相比,丁酸钠能够显著提高低蛋白质饲粮组肉鸡腿肌脂肪含量,但胸肌和腹部脂肪含量差异不显著。造成低蛋白质饲粮组肉鸡脂肪沉积差异的原因可能是由于低蛋白质饲粮组饲粮能蛋比较高,多余的能量更易转化为脂肪;另外,与胸肌和腹部脂肪组织相比,丁酸钠可能选择性地增加腿肌IRβ的表达,增强其对葡萄糖的吸收,从而提高低蛋白质饲粮组腿肌脂肪含量。

4 小结与展望

综上所述,丁酸钠能够通过调控组蛋白乙酰化、GPR等多条途径保护肠道屏障功能,在肉鸡上具有促生长、抗应激等多种作用,有替代抗生素的潜力。但目前丁酸钠对肉鸡肠道屏障上的基础研究较少,这限制了丁酸钠的推广和应用。下一步的研究重点建议放在:1)研究丁酸钠调控肉鸡肠道黏膜细胞(上皮细胞、潘氏细胞、杯状细胞、巨噬细胞和树突状细胞)和紧密连接蛋白的机制,以及诱导T细胞、B细胞分化的机制等。2)根据丁酸钠的作用机制,筛选合适的饲料添加剂与之组合,提高肉鸡生长性能和抗病能力。例如将丁酸钠(提高线粒体抗氧化性能)与烟酰胺(增强线粒体功能)组合抗应激和提高肌肉品质。3)研究不同释放时间,不同含量的包被丁酸钠,以及包被丁酸钠与饲粮能量、蛋白质水平之间的互作对肉鸡生产性能和肠道健康的影响。

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