中药防控产肠毒素大肠杆菌感染仔猪腹泻的研究进展

doi:10.16431/j.cnki.1671-7236.2024.12.037

摘要/Abstract

摘要： 产肠毒素大肠杆菌(ETEC)造成的仔猪腹泻严重影响仔猪健康，是造成仔猪死亡的重要病因，给生猪养殖行业带来巨大的经济损失。ETEC的主要毒力因子是肠毒素和黏附素，肠毒素主要分为耐热肠毒素和不耐热肠毒素，其通过不同方式作用于小肠上皮细胞表面，引起小肠内水和电解质积蓄及代谢紊乱，导致仔猪腹泻，而黏附素则促进ETEC在仔猪小肠上皮细胞定植。目前的疫苗只包括部分菌毛黏附素、肠毒素，免疫效果不全面、缺乏广谱性。现阶段在临床应用中中药效果良好，能大幅度提升感染仔猪存活率、抑制ETEC生长和毒力基因表达、缓解感染仔猪的炎症反应、减少肠道损伤、提升感染仔猪的免疫力及调控ETEC感染造成的仔猪肠道微生物的平衡、调控仔猪肠道化学屏障，从多方面防控ETEC感染。在饲料端全面禁抗背景下，消费者越来越青睐绿色、无抗的生猪产品，而兽用中药为仔猪腹泻病的临床防控提供了新思路和新策略。因此，笔者对ETEC入侵仔猪肠道的致病机理以及中药在该疾病治疗上的应用和治疗效果进行总结概括。

关键词: 产肠毒素大肠杆菌(ETEC); 中药; 腹泻; 肠毒素

Abstract: Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) seriously affects the health of piglets,which is an important cause of death of piglets,and brings huge economic losses to pig breeding industry.The main virulence factors of ETEC are enterotoxin and adhesin.Enterotoxin is mainly divided into heat-stable enterotoxin and heat-labile enterotoxin,which act on the surface of small intestinal epithelial cells in different ways,causing water and electrolyte accumulation and metabolic disorders in small intestine,resulting in diarrhea of piglets,while adhesin promotes the colonization of ETEC in small intestinal epithelial cells of piglets.The current vaccines only include part of fimbrial adhesin and enterotoxin,and the immune effect is not comprehensive and lacks broad spectrum.At present,the effect of traditional Chinese medicine in clinical application is good,which can greatly improve the survival rate of infected piglets,inhibit the growth of ETEC and the expression of virulence genes,alleviate the inflammatory response,reduce intestinal damage,improve the immunity of infected piglets,regulate the balance of intestinal microorganisms caused by ETEC infection,and regulate the intestinal chemical barrier of piglets，to prevent and control ETEC infection from various aspects.Under the background of total forage prohibition,consumers are increasingly favoring green and non-resistant pig products,and veterinary Chinese medicine provides new ideas and strategies for the clinical prevention and control of piglet diarrhea disease. Therefore,the author summarized the pathogenic mechanism of ETEC invasion into the intestinal tract of piglets and the application and therapeutic effect of Chinese medicine in the treatment of this disease.

Key words: enterotoxigenic Escherichia coli (ETEC); traditional Chinese medicine; diarrhea; enterotoxin

中图分类号:

S858.292

杨植, 王煜轩, 王之文, 芦烘德, 王禄皓, 何至远, 董虹. 中药防控产肠毒素大肠杆菌感染仔猪腹泻的研究进展[J]. 中国畜牧兽医, 2024, 51(12): 5507-5517.

YANG Zhi, WANG Yuxuan, WANG Zhiwen, LU Hongde, WANG Luhao, HE Zhiyuan, DONG Hong. Research Progress on Prevention and Control of Diarrhea of Piglets Infected with ETEC by Traditional Chinese Medicine[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(12): 5507-5517.

参考文献

[1] LIU G，GU K，WANG F，et al.Tryptophan ameliorates barrier integrity and alleviates the inflammatory response to enterotoxigenic Escherichia coli K88 through the CaSR/Rac1/PLC-γ1 signaling pathway in porcine intestinal epithelial cells[J].Frontiers in Immunology，2021，12:748497.
[2] DUBREUIL J D.Pig vaccination strategies based on enterotoxigenic Escherichia coli toxins[J].Brazilian Journal of Microbiology，2021，52(4):2499-2509.
[3] 吕林芬, 庞胜美, 李保良，等.仔猪产肠毒素大肠杆菌疫苗的研究进展[J].河南农业科学, 2023, 52(5):1-8.LYU L F, PANG S M, LI B L, et al.Research progress on enterotoxigenic Escherichia coli vaccine for piglets[J].Henan Agricultural Sciences, 2023, 52(5):1-8.(in Chinese)
[4] 赵浩飞, 赵红, 徐永平，等.猪源产肠毒素大肠杆菌疫苗的研究进展[J].畜牧与兽医, 2021, 53(11):141-144.ZHAO H F, ZHAO H, XU Y P, et al.Research progress of swine enterotoxigenic Escherichia coli vaccine [J].Animal Husbandry and Veterinary Medicine, 2021, 53(11):141-144.(in Chinese)
[5] DUAN Q D，WU W W，PANG S M.ETEC引起断奶仔猪腹泻新型多价表位疫苗的研究[J].中国预防兽医学报, 2021, 43(1):111.DUAN Q D，WU W W，PANG S M.ETEC, a novel multivalent epitope vaccine for diarrhea in weaned piglets[J].Chinese Journal of Preventive Veterinary Medicine, 2021, 43(1):111.(in Chinese)
[6] 王晓丽.猪源产肠毒素大肠杆菌的研究概况[J].猪业观察, 2020, 43(4):27-28.WANG X L.Research overview of enterotoxigenic Escherichia coli from swine[J].Pig Industry Observation, 2020, 43(4):27-28.(in Chinese)
[7] 张翥, 王明周, 朱燕，等.香砂六君子汤对产肠毒素性大肠杆菌诱导断奶腹泻仔猪的腹泻指数、生长性能和小肠黏膜发育的影响[J].中国畜牧杂志, 2021, 57(8):242-245.ZHANG Z, WANG M Z, ZHU Y，et al.Effects of Xiangsha Liujunzi decoction on diarrhea index, growth performance and intestinal mucosal development of weaned piglets with diarrhea induced by enterotoxigenic Escherichia coli[J].Chinese Journal of Animal Science, 2021, 57(8):242-245.(in Chinese)
[8] 谭亚飞.乳猪腹泻的中医解析及防控[J].中国动物保健, 2019, 21(8):29-30.TAN Y F.Analysis and prevention and control of piglet diarrhea in traditional Chinese medicine[J]. China Animal Health, 2019, 21(8):29-30.(in Chinese)
[9] 何建起.用中医方法辨证施治仔猪腹泻[J].中国猪业, 2012, 7(1):47-48.HE J Q.Treatment of piglet diarrhea with traditional Chinese medicine[J].China Swine Industry, 2012, 7(1):47-48.(in Chinese)
[10] 袁小花, 曹凤国.中药治疗猪腹泻效果观察[J].中兽医学杂志, 2022, 251(10):22-25.YUAN X H, CAO F G.Observation on the effect of traditional Chinese medicine in the treatment of pig diarrhea[J].Chinese Journal of Traditional Veterinary Science, 2022, 251(10):22-25.(in Chinese)
[11] 马斌.猪源大肠杆菌小鼠腹泻模型的构建及防治用中药复方制剂的研制[D].长春：吉林农业大学, 2021.MA B.Construction of diarrhea model of pig-derived Escherichia coli in mice and development of traditional Chinese medicine compound preparations for prevention and treatment[D].Changchun：Jilin Agricultural University, 2021.(in Chinese)
[12] 邹少钧.栀子柏皮汤及黄秦仔泻宁治疗仔猪大肠杆菌腹泻的研究[D].哈尔滨：哈尔滨商业大学, 2020.ZOU S J.Study on Zhizi Baipi decoction and Huangqin Zixiening in the treating E.coli diarrhea in piglets[D].Harbin：Harbin University of Commerce, 2020.(in Chinese)
[13] 夏方.中药地翁颗粒治疗仔猪白痢的有效性和安全性研究[D].长春：吉林大学, 2015.XIA F.Study on the efficacy and safety of Diweng granule in the treatment of piglet dysentery[D].Changchun：Jilin University, 2015.(in Chinese)
[14] 刘筱.中药赤黄止痢颗粒治疗仔猪白痢的药效学和安全性研究[D].杨凌：西北农林科技大学, 2018.LIU X.Study on the pharmacodynamics and safety of Chihuang antidysenteric granules in the treatment of white dysentery in piglets[D].Yangling：Northwest A&F University, 2018.(in Chinese)
[15] 张恒.中药“复方黄连散”防治仔猪大肠杆菌性腹泻机理的研究[D].北京：中国农业科学院, 2010.ZHANG H.Explore the mechanism of prevention and treatment of Chinese herbal medicine “Fufang Huangliansan” on Escherichia coli-induced diarrhea of piglet[D]. Beijing：Chinese Academy of Agricultural Sciences, 2010.(in Chinese)
[16] 谷巍, 王丽荣, 孙明杰, 等.嗜酸乳杆菌发酵的复方中药对腹泻小鼠肠道菌群和结构的影响[J].中兽医医药杂志, 2020, 39(1):8-13.GU W, WANG L R, SUN M J, et al.Effects of traditional Chinese medicine fermented by Lactobacillus on intestinal flora and structure of diarrhea mice[J].Journal of Chinese Traditional Veterinary, 2020, 39(1):8-13.(in Chinese)
[17] 孔春梅, 刘小宝, 宋洁, 等.抗大肠杆菌耐热肠毒素中药方剂的筛选[J].中国兽医杂志, 2008，11:64-66.KONG C M, LIU X B, SONG J, et al.Screening of traditional Chinese medicine prescriptions for anti-E.coli heat-resistant enterotoxin[J]. Chinese Journal of Veterinary Medicine, 2008, 11:64-66.(in Chinese)
[18] GUO P, WANG Z, LV X, et al.Changyanning regulates gut microbiota and metabolism to ameliorate intestinal injury induced by ETEC K88[J].Frontiers in Microbiology，2023，14:1098818.
[19] 刘晓曦.加味葛根芩连汤对湿热泄泻仔猪肠道和体外肠上皮细胞损伤的调控机理[D].北京：中国农业大学, 2017.LIU X X.Regulation mechanism of Jiawei Gegen Qinlian decoction on intestinal and in vitro intestinal epithelial cell injury in piglets with damp-heat diarrhea[D].Beijing：China Agricultural University, 2017.(in Chinese)
[20] 满建诚.饲料中添加白头翁散对仔猪大肠埃希氏菌性腹泻防治试验[J].猪业科学, 2023, 40(7):61-63.MAN J C.Experiment on prevention and treatment of Escherichia coli diarrhea in piglets by adding Pulsatilla powder to feed[J].Swine Industry Science, 2023, 40(7):61-63.(in Chinese)
[21] 黄登桂.猪大肠杆菌耐热肠毒素损伤肠上皮完整性的机制研究[D].广州：华南农业大学, 2019.HUNAG D G.Study on the mechanism of heat-resistant enterotoxin of porcine E.coli damaging intestinal epithelial integrity[D].Guangzhou：South China Agricultural University, 2019.(in Chinese)
[22] 赵新荣.茶黄素-3'-没食子酸酯对ETEC感染IPEC-J2细胞的拮抗效果及作用机制研究[D].哈尔滨：东北农业大学, 2024.ZHAO X R.The intervention effect and mechanism of theaflavin-3'-gallate on ETEC-infected IPEC-J2 cells[D].Harbin：Northeast Agricultural University, 2024.(in Chinese)
[23] 王文文.仔猪产肠毒素大肠杆菌(ETEC)F4ac受体基因的鉴定及功能验证[D].北京：中国农业大学, 2016.WANG W W.Identification and functional verification of F4ac receptor gene in enterotoxigenic Escherichia coli (ETEC)[D].Beijing：China Agricultural University, 2016.(in Chinese)
[24] DUAN Q, WU W, PANG S, et al.Coimmunization with two enterotoxigenic Escherichia coli (ETEC) fimbrial multiepitope fusion antigens induces the production of neutralizing antibodies against five ETEC fimbriae (F4, F5, F6, F18, and F41)[J].Applied and Environmental Microbiology，2020，86(24):e00217-20.
[25] DUBREUIL J D, ISAACSON R E, SCHIFFERLI D M.Animal enterotoxigenic Escherichia coli [J].Ecosal Plus Journal Homepage, 2016, 7(1):2016.
[26] 权国梅.F4ac⁺产肠毒素大肠杆菌锌转运系统ZnuACB功能探究[D].扬州：扬州大学, 2021.QUAN G M.Study on the function of ZnuACB in F4ac⁺ enterotoxigenic Escherichia coli zinc transport system[D].Yangzhou：Yangzhou University, 2021.(in Chinese)
[27] 盛宣博.枯草芽孢杆菌对产肠毒素性大肠杆菌攻毒兔肠道功能的影响[D].哈尔滨：东北农业大学, 2022.SHENG X B.Effects of Bacillus subtilis on intestinal function of rabbits challenged with enterotoxigenic Escherichia coli[D].Harbin：Northeast Agricultural University, 2022.(in Chinese)
[28] 李雪滢.白芍总苷及芍药苷对ETEC诱导的猪肠上皮细胞炎性损伤的调控作用[D].重庆：西南大学, 2021.LI X Y.Effects of total glucosides of paeony and paeoniflorin on expression of inflammatory damage of porcine intestinal epithelial cells induced by ETEC[D].Chongqing：Southwest University, 2021.(in Chinese)
[29] 刘晓曦, 张继东, 马云飞, 等.葛根素、黄芩苷和盐酸小檗碱对肠毒素大肠杆菌(ETEC)生长及毒力相关基因mRNA表达的影响[J].中国兽医杂志, 2019, 55(8):46-48.LIU X X, ZHANG J D, MA Y F，et al.Effects of puerarin, baicalin and berberine hydrochloride on the regulation of enterotoxigenic Escherichia coli growth and its toxin gene expressions[J].Chinese Journal of Veterinary Medicine, 2019, 55(8):46-48.(in Chinese)
[30] 董世山.中药对仔猪腹泻的防治作用及其机理研究[D].北京：中国农业科学院, 2005.DONG S S.The effects and mechanisms of several Chinese herbal medicine on piglet’s diarrhea[D].Beijing：Chinese Academy of Agricultural Sciences, 2005.(in Chinese)
[31] 吴仲元, 师亚倩, 周华林, 等.黄芩苷铜的优化合成及其对猪源大肠杆菌K88的抗菌作用[J].中国兽医杂志, 2022, 58(5):71-74.WU Z Y，SHI Y Q, ZHOU H L, et al.Optimized synthesis of baicalin copper and its antibacterial effect on porcine Escherichia coli K88[J].Chinese Journal of Veterinary Medicine, 2022, 58(5):71-74.(in Chinese)
[32] 曹冶, 谢晶, 康润敏, 等.中药诃子、余甘子对奶牛乳房炎病原菌体外抑制作用的研究[J].中国奶牛, 2023, 2:39-42.CAO Y, XIE J, KANG R M, et al.In vitro inhibitory of Terminalia chebula and Phyllanthus emblica on pathogenic bacteria of mastitis in dairy cows[J].China Dairy Cattle, 2023, 2:39-42.(in Chinese)
[33] 梁正, 徐强, 张倩, 等.五倍子化学成分和药理作用的研究进展[J].中草药, 2022, 53(18):5908-5919.LIANG Z, XU Q, ZHANG Q, et al.Advances in studies on chemical constituents and pharmacological effects of gallnut[J].Chinese Traditional and Herbal Drugs, 2022, 53(18):5908-5919.(in Chinese)
[34] 吕欣彧.山茱萸—牡丹皮抗LT型大肠杆菌致仔猪腹泻的作用研究[D].哈尔滨：哈尔滨商业大学, 2020.LYU X Y.Effect of cornus officinalis-cortex moutan on piglet diarrhea caused by LT enterotoxigenic Escherichia coli [D].Harbin：Harbin University of Commerce, 2020.(in Chinese)
[35] 王聪.罗伊氏乳杆菌与乌梅共发酵产物对仔猪大肠杆菌性腹泻的疗效评价[D].长春：吉林农业大学, 2018.WANG C.Therapeutic evaluation of fermentation products of dark plum and Lactobacillus reuteri on Escherichia coli-induced diarrhea in piglets[D].Changchun：Jilin Agricultural University, 2018.(in Chinese)
[36] 韩阳春.白芍总苷对ETEC致腹泻仔猪肠道基因转录组学变化及炎性损伤的调控作用[D].重庆：西南大学, 2022.HAN Y C.Regulation of total glucosides of paeony on intestinal gene transcriptomics changes and inflammatory injury in diarrhea piglets induced by ETEC[D].Chongqing：Southwest University, 2022.(in Chinese)
[37] 唐翠娥.原花青素与益生菌抗ETEC诱导的腹泻作用及其机制研究[D].武汉：华中农业大学, 2019.TANG C E.The effect of proanthocyanidins and probiotics on enterotoxigenic Escherichia coli induced diarrhea and its underlying mechanism research[D].Wuhan：Huazhong Agricultural University, 2019.(in Chinese)
[38] 李盼.中草药复合制剂对仔猪大肠杆菌性腹泻治疗效果研究[D].长春：吉林农业大学, 2015.LI P.Study on the therapeutic effect of Chinese herbal compound preparation for Escherichia coli-induced diarrhea of piglet[D].Changchun：Jilin Agricultural University, 2015.(in Chinese)
[39] 索占伟, 胡格, 刘钟杰, 等.大肠杆菌热敏肠毒素对肠黏膜微血管内皮细胞的影响及白头翁素对其保护作用的研究[J].中国兽医杂志, 2009, 45(1):33-35.SUO Z W, HU G, LIU Z J, et al.Study on the effect of Escherichia coli heat-sensitive enterotoxin on intestinal mucosal microvascular endothelial cells and the protective effect of anemonin[J].Chinese Journal of Veterinary Medicine, 2009, 45(1):33-35.(in Chinese)
[40] DENG Y, HAN X, TANG S, et al.Magnolol and honokiol attenuate apoptosis of enterotoxigenic Escherichia coli-induced intestinal epithelium by maintaining secretion and absorption homeostasis and protecting mucosal integrity[J].Medical Science Monitor，2018，24:3348-3356.
[41] 乐美芳.小檗碱对断奶仔猪生长性能和肠道健康的影响[D].广州：华南农业大学, 2023.LE M F.Effects of berberine on growth performance and intestinal health in weaned piglets[D].Guangzhou：South China Agricultural University, 2023.(in Chinese)
[42] 黄静.ETEC感染对猪肠道上皮细胞的炎性损伤作用及甘草多糖的干预效果研究[D].重庆：西南大学, 2020.HUANG J.Effect of ETEC infection on inflammatory injury of porcine intestinal epithelial cells and the intervention effect of Glycyrrhiza polysaccharide[D].Chongqing：Southwest University, 2020.(in Chinese)
[43] 肖乐, 刘峻源, 曾雯玉, 等.基于微生物组和宿主转录组整合分析香砂六君子汤对ETEC诱导断奶腹泻仔猪回肠损伤的调控机制[J].畜牧兽医学报, 2024, 55(2):797-808.XIAO L, LIU J Y, ZENG W Y, et al.Microbiome and transcriptome analyses reveale the regulatory mechanism of Xiangsha Liujunzi decoction on ileal injury induced by ETEC in weaned piglets with diarrhea[J].Acta Veterinaria et Zootechnica Sinica, 2024, 55(2):797-808.(in Chinese)
[44] 曾雯玉.白芍总苷及甘草多糖对ETEC诱导腹泻仔猪肠道黏膜免疫机能和肠道微生物菌群的影响[D].重庆：西南大学, 2023.ZENG W Y.Regulation of total glucosides of paeony on intestinal transcriptome changes inflammatory injury in diarrhea piglets induced by ETEC[D].Chongqing：Southwest University, 2023.(in Chinese)
[45] FU S, ZUANG F, GUO L，et al.Effect of baicalin-aluminum complexes on fecal microbiome in piglets[J].International Journal of Molecular Sciences.2019，20(10):2390.
[46] KUHN K A, PEDRAZA I, DEMORUELLE M K.Mucosal immune responses to microbiota in the development of autoimmune disease[J].Rheumatic Disease Clinics of North America, 2014，40(4):711-725.
[47] SUN H, NI X, SONG X，et al.Fermented Yupingfeng polysaccharides enhance immunity by improving the foregut microflora and intestinal barrier in weaning rex rabbits[J].Applied Microbiology and Biotechnology, 2016，100(18):8105-8120.
[48] WANG X, HUANG S, ZHANG M，et al.Gegen Qinlian decoction activates AhR/IL-22 to repair intestinal barrier by modulating gut microbiota-related tryptophan metabolism in ulcerative colitis mice[J].Journal of Ethnopharmacology, 2023，302:115919.
[49] GAO X, GUO M, ZHANG Z，et al.Baicalin promotes the bacteriostatic activity of lysozyme on S.aureus in mammary glands and neutrophilic granulocytes in mice[J].OncoTargets and Therapy, 2017，8(12):19894-19901.
[50] 张鹤平, 刘建钗, 许剑琴, 等.白苦败痢散治疗仔猪大肠杆菌性腹泻的临床效果[J].中国兽医杂志, 2021, 57(10):82-87.ZHANG H P, LIU J C, XU J Q, et al.Clinical efficacy of Baikubailisan for treatment of Escherichia coli diarrhea in piglets[J].Chinese Journal of Veterinary Medicine, 2021, 57(10):82-87.(in Chinese)
[51] 卢伟.黄芩与鼠李糖乳杆菌发酵产物对仔猪大肠杆菌腹泻治疗效果研究[D].长春：吉林农业大学, 2017.LU W.Study on therapy effect of fermentation products of radix scutellariae and Lactobacillus rhamnosus on Escherichia coli-induced diarrhea in piglets[D].Changchun：Jilin Agricultural University, 2017.(in Chinese)
[52] 刘勇亮, 陈波, 刘明刚, 等.连梅止痢中药制剂对大肠埃希菌K88感染仔猪的疗效[J].浙江农业学报, 2016, 28(9):1493-1500.LIU Y L, CHEN B, LIU M G, et al.Effect of Lianmei dysentery Chinese hebal preparation on weaned piglet diarrhea by Escherichia coli (K88) experimental infection[J]. Acta Agriculturae Zhejiangensis, 2016, 28(9):1493-1500.(in Chinese)