Research Progress in Treatment and Anti-inflammatory Molecular Mechanism of Cow Mastitis

doi:10.13560/j.cnki.biotech.bull.1985.2021-0170

Abstract

Abstract:

Cow mastitis is an inflammatory reaction of mammary tissue caused by pathogenic microorganisms infection,blood circulation disorders,physicochemical stimulation,etc. It is one of the common diseases of dairy cows,which seriously affects the economic benefits of the dairy industry. In recent years,aiming at continuously exploring and developing treatment methods for cow mastitis,domestic and foreign scholars have studied the roles and molecular mechanisms of various substances on bovine mammary gland inflammation. This paper summarized the pathogenic causes of cow mastitis,and focused on the latest research progress of bioactive substances,mineral elements,vitamins and biological agents in the treatment and anti-inflammatory molecular mechanism of cow mastitis,aiming to provide a reference for the studies of the prevention and precise treatment of mastitis in dairy cow.

Key words: dairy cows, mastitis, anti-inflammatory, active substance, biological treatment

WANG Jin-peng, LUORENG Zhuo-ma, WANG Xing-ping, YANG Jian, JIA Li, MA Yun, WEI Da-wei. Research Progress in Treatment and Anti-inflammatory Molecular Mechanism of Cow Mastitis[J]. Biotechnology Bulletin, 2021, 37(12): 212-219.

Figures/Tables 2

References 48

[1]	Ashraf A, Imran M. Causes, types, etiological agents, prevalence, diagnosis, treatment, prevention, effects on human health and future aspects of bovine mastitis[J]. Anim Health Res Rev, 2020, 21(1):36-49. doi: 10.1017/S1466252319000094 URL
[2]	Tucker IG, Jain R, Alawi F, et al. Translational studies on a ready-to-use intramuscular injection of penethamate for bovine mastitis[J]. Drug Deliv Transl Res, 2018, 8(2):317-328. doi: 10.1007/s13346-017-0388-1 URL
[3]	高瑞娟, 王纯洁, 敖日格乐, 等. 蒙药成份复方对乳腺炎模型小鼠免疫功能的影响[J]. 中国农业大学学报, 2018, 23(1):106-112.
	Gao RJ, Wang CJ, Aorigele, et al. Immunoregulation effect of Mongolian medicine composition compounds on mastitis model mice[J]. J China Agric Univ, 2018, 23(1):106-112.
[4]	Oviedo-Boyso J, Valdez-Alarcón JJ, Cajero-Juárez M, et al. Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis[J]. J Infect, 2007, 54(4):399-409. pmid: 16882453
[5]	Le Roux Y, Laurent F, Moussaoui F. Polymorphonuclear proteolytic activity and milk composition change[J]. Vet Res, 2003, 34(5):629-645. doi: 10.1051/vetres:2003021 URL
[6]	Klaas IC, Zadoks RN. An update on environmental mastitis:Challenging perceptions[J]. Transbound Emerg Dis, 2018, 65(Suppl 1):166-185.
[7]	Wellnitz O, Bruckmaier RM. The innate immune response of the bovine mammary gland to bacterial infection[J]. Vet J, 2012, 192(2):148-152. doi: 10.1016/j.tvjl.2011.09.013 pmid: 22498784
[8]	Khan MZ, Khan A, Xiao J, et al. Role of the JAK-STAT pathway in bovine mastitis and milk production[J]. Animals(Basel), 2020, 10(11):2107.
[9]	姚学萍, 杨德英, 杨洪森, 等. 乳头管灌注金黄色葡萄球菌对家兔血清中酶活性的影响[J]. 中国畜牧兽医, 2010, 37(2):59-62.
	Yao XP, Yang DY, Yang HS, et al. The effects on the activities of enzymes in serum by infusing Staphylococcus aureus via teat duct in rabbits[J]. China Animal Husb Vet Med, 2010, 37(2):59-62.
[10]	Wellnitz O, Arnold ET, Bruckmaier RM. Lipopolysaccharide and lipoteichoic acid induce different immune responses in the bovine mammary gland[J]. J Dairy Sci, 2011, 94(11):5405-5412. doi: 10.3168/jds.2010-3931 pmid: 22032363
[11]	Sarwar T, Ishqi HM, Rehman SU, et al. Caffeic acid binds to the minor groove of calf Thymus DNA:a multi-spectroscopic, thermodynamics and molecular modelling study[J]. Int J Biol Macromol, 2017, 98:319-328. doi: 10.1016/j.ijbiomac.2017.02.014 URL
[12]	Liu M, Song S, Li H, et al. The protective effect of caffeic acid against inflammation injury of primary bovine mammary epithelial cells induced by lipopolysaccharide[J]. J Dairy Sci, 2014, 97(5):2856-2865. doi: 10.3168/jds.2013-7600 URL
[13]	Ye YY, Pei LX, Ding J, et al. Effects of Platycodin D on S100A8/A9-induced inflammatory response in murine mammary carcinoma 4T1 cells[J]. Int Immunopharmacol, 2019, 67:239-247. doi: 10.1016/j.intimp.2018.12.008 URL
[14]	Wang Y, Zhang X, Wei Z, et al. Platycodin D suppressed LPS-induced inflammatory response by activating LXRα in LPS-stimulated primary bovine mammary epithelial cells[J]. Eur J Pharmacol, 2017, 814:138-143. doi: 10.1016/j.ejphar.2017.07.037 URL
[15]	He XX, Liu WJ, Shi MY, et al. Docosahexaenoic acid attenuates LPS-stimulated inflammatory response by regulating the PPARγ/NF-κB pathways in primary bovine mammary epithelial cells[J]. Res Vet Sci, 2017, 112:7-12. doi: 10.1016/j.rvsc.2016.12.011 URL
[16]	Li J, Yin P, Gong P, et al. 8-Methoxypsoralen protects bovine mammary epithelial cells against lipopolysaccharide-induced inflammatory injury via suppressing JAK/STAT and NF-κB pathway[J]. Microbiol Immunol, 2019, 63(10):427-437. doi: 10.1111/mim.v63.10 URL
[17]	Zheng C, Lin JF, Lin ZH, et al. Sodium houttuyfonate alleviates post-infarct remodeling in rats via AMP-activated protein kinase pathway[J]. Front Pharmacol, 2018, 9:1092. doi: 10.3389/fphar.2018.01092 URL
[18]	Wang W, Hu X, Shen P, et al. Sodium houttuyfonate inhibits LPS-induced inflammatory response via suppressing TLR4/NF-ĸB signaling pathway in bovine mammary epithelial cells[J]. Microb Pathog, 2017, 107:12-16. doi: 10.1016/j.micpath.2017.03.011 URL
[19]	Wang JJ, Guo CM, Wei ZK, et al. Morin suppresses inflammatory cytokine expression by downregulation of nuclear factor-κB and mitogen-activated protein kinase(MAPK)signaling pathways in lipopolysaccharide-stimulated primary bovine mammary epithelial cells[J]. J Dairy Sci, 2016, 99(4):3016-3022. doi: 10.3168/jds.2015-10330 URL
[20]	Wei ZK, Zhou ES, Guo CM, et al. Thymol inhibits Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation[J]. Microb Pathog, 2014, 71/72:15-19. doi: 10.1016/j.micpath.2014.01.004 URL
[21]	Liang D, Li F, Fu Y, et al. Thymol inhibits LPS-stimulated inflammatory response via down-regulation of NF-κB and MAPK signaling pathways in mouse mammary epithelial cells[J]. Inflammation, 2014, 37(1):214-222. doi: 10.1007/s10753-013-9732-x URL
[22]	Lu ZB, Liu SH, Ou JY, et al. Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124[J]. Toxicol Appl Pharmacol, 2020, 407:115252. doi: 10.1016/j.taap.2020.115252 URL
[23]	Zhang JL, Zhang Y, Huang HL, et al. Forsythoside A inhibited S. aureus stimulated inflammatory response in primary bovine mammary epithelial cells[J]. Microb Pathog, 2018, 116:158-163. doi: 10.1016/j.micpath.2018.01.002 URL
[24]	Wang FG, Chen SX, Jiang YW, et al. Effects of ammonia on apoptosis and oxidative stress in bovine mammary epithelial cells[J]. Mutagenesis, 2018, 33(4):291-299. doi: 10.1093/mutage/gey023 URL
[25]	Wang FG, Zhao Y, Chen SX, et al. Astragaloside IV alleviates ammonia-induced apoptosis and oxidative stress in bovine mammary epithelial cells[J]. Int J Mol Sci, 2019, 20(3):600. doi: 10.3390/ijms20030600 URL
[26]	Ma YF, Zhao L, Coleman DN, et al. Tea polyphenols protect bovine mammary epithelial cells from hydrogen peroxide-induced oxidative damage in vitro by activating NFE2L2/HMOX1 pathways[J]. J Dairy Sci, 2019, 102(2):1658-1670. doi: S0022-0302(18)31121-4 pmid: 30594360
[27]	Gao XJ, Zhang ZC, Li Y, et al. Selenium deficiency facilitates inflammation following S. aureus infection by regulating TLR2-related pathways in the mouse mammary gland[J]. Biol Trace Elem Res, 2016, 172(2):449-457. doi: 10.1007/s12011-015-0614-y URL
[28]	Wang H, Bi CL, Wang YJ, et al. Selenium ameliorates Staphylococcus aureus-induced inflammation in bovine mammary epithelial cells by inhibiting activation of TLR2, NF-κB and MAPK signaling pathways[J]. BMC Vet Res, 2018, 14(1):1-8. doi: 10.1186/s12917-017-1323-x URL
[29]	Zhang ZB, Guo YF, Li CY, et al. Selenium influences mmu-miR-155 to inhibit inflammation in Staphylococcus aureus-induced mastitis in mice[J]. Food Funct, 2019, 10(10):6543-6555. doi: 10.1039/C9FO01488H URL
[30]	Mathur P, Jha S, Ramteke S, et al. Pharmaceutical aspects of silver nanoparticles[J]. Artif Cells Nanomed Biotechnol, 2018, 46(sup1):115-126. doi: 10.1080/21691401.2017.1414825 URL
[31]	Kalińska A, Jaworski S, Wierzbicki M, et al. Silver and copper nanoparticles-an alternative in future mastitis treatment and prevention?[J]. Int J Mol Sci, 2019, 20(7):E1672.
[32]	Wei ZK, Fu YH, Zhou ES, et al. Effects of niacin on Staphylococcus aureus internalization into bovine mammary epithelial cells by modulating NF-κB activation[J]. Microb Pathog, 2014, 71/72:62-67. doi: 10.1016/j.micpath.2014.03.005 URL
[33]	董淑慧, 王加启, 李发弟, 等. 奶牛血清中维生素A和维生素E含量的测定及其与牛乳中体细胞数的相关性[J]. 甘肃农业大学学报, 2013, 48(1):19-25.
	Dong SH, Wang JQ, Li FD, et al. Simultaneous determination method of vitamin A and vitamin E in dairy cow serum by HPLC and relationship with SCC in milk[J]. J Gansu Agric Univ, 2013, 48(1):19-25.
[34]	Guo WJ, Liu JX, Li W, et al. Niacin alleviates dairy cow mastitis by regulating the GPR109A/AMPK/NRF2 signaling pathway[J]. Int J Mol Sci, 2020, 21(9):3321. doi: 10.3390/ijms21093321 URL
[35]	Du HS, Wang C, Wu ZZ, et al. Effects of rumen-protected folic acid and rumen-protected sodium selenite supplementation on lactation performance, nutrient digestion, ruminal fermentation and blood metabolites in dairy cows[J]. J Sci Food Agric, 2019, 99(13):5826-5833. doi: 10.1002/jsfa.v99.13 URL
[36]	刘雪琴, 王迪, 米思远, 等. 叶酸补饲对隐性乳房炎奶牛免疫力及产奶性状相关基因表达的影响[J]. 畜牧兽医学报, 2020, 51(11):2731-2742.
	Liu XQ, Wang D, Mi SY, et al. The effect of folic acid supplementation on the expression of genes related to immunity and milking traits in subclinical mastitis cows[J]. Chin J Animal Vet Sci, 2020, 51(11):2731-2742.
[37]	Bouwstra RJ, Nielen M, Stegeman JA, et al. Vitamin E supplementation during the dry period in dairy cattle. Part I:Adverse effect on incidence of mastitis postpartum in a double-blind randomized field trial[J]. J Dairy Sci, 2010, 93(12):5684-5695. doi: 10.3168/jds.2010-3159 pmid: 21094740
[38]	Alva-Murillo N, Téllez-Pérez AD, Medina-Estrada I, et al. Modulation of the inflammatory response of bovine mammary epithelial cells by cholecalciferol(vitamin D)during Staphylococcus aureus internalization[J]. Microb Pathog, 2014, 77:24-30. doi: 10.1016/j.micpath.2014.10.006 URL
[39]	刘豪. 生物制剂在奶牛乳腺炎防治上的应用[J]. 中国畜牧兽医文摘, 2017, 33(9):228.
	Liu H. Application of biological agents in prevention and treatment of dairy cow mastitis[J]. Chinese Abstracts of Animal Husbandry and Veterinary Medicine, 2017, 33(9):228.
[40]	李连彬. 菌丝霉素源抗菌肽对金黄色葡萄球菌乳腺炎的防治及其耐药产生机制的研究[D]. 杨凌:西北农林科技大学, 2018.
	Li LB. Effect of plectasin-derived antimicrobial peptides on S. aureus mastitis and the study on mechanism of antimicrobial peptides resistance development[D]. Yangling:Northwest A & F University, 2018.
[41]	Ragland SA, Criss AK. From bacterial killing to immune modulation:Recent insights into the functions of lysozyme[J]. PLoS Pathog, 2017, 13(9):e1006512. doi: 10.1371/journal.ppat.1006512 URL
[42]	Bouchard DS, Seridan B, Saraoui T, et al. Lactic acid bacteria isolated from bovine mammary microbiota:potential allies against bovine mastitis[J]. PLoS One, 2015, 10(12):e0144831. doi: 10.1371/journal.pone.0144831 URL
[43]	Cormican P, Meade KG, Cahalane S, et al. Evolution, expression and effectiveness in a cluster of novel bovine β-defensins[J]. Immunogenetics, 2008, 60(3/4):147-156. doi: 10.1007/s00251-007-0269-8 URL
[44]	Báez-Magaña M, Ochoa-Zarzosa A, Alva-Murillo N, et al. Lipid-rich extract from Mexican avocado seed(Persea americana var. drymifolia)reduces Staphylococcus aureus internalization and regulates innate immune response in bovine mammary epithelial cells[J]. J Immunol Res, 2019, 2019:7083491.
[45]	Kościuczuk EM, Lisowski P, Jarczak J, et al. Expression patterns of β-defensin and cathelicidin genes in parenchyma of bovine mammary gland infected with coagulase-positive or coagulase-negative Staphylococci[J]. BMC Vet Res, 2014, 10(1):246. doi: 10.1186/s12917-014-0246-z URL
[46]	孙怀昌, 于锋, 苏建华, 等. 人溶菌酶基因治疗奶牛乳腺炎的初步研究[J]. 畜牧兽医学报, 2004, 35(2):227-232.
	Sun HC, Yu F, Su JH, et al. Preliminary studies on gene therapy for dairy cow mastitis using human lysozyme gene[J]. Chin J Animal Vet Sci, 2004, 35(2):227-232.
[47]	Donovan DM, Lardeo M, Foster-Frey J. Lysis of staphylococcal mastitis pathogens by bacteriophage phi11 endolysin[J]. FEMS Microbiol Lett, 2006, 265(1):133-139. pmid: 17054440
[48]	Assis BS, Germon P, Silva AM, et al. Lactococcus lactis V7 inhibits the cell invasion of bovine mammary epithelial cells by Escherichia coli and Staphylococcus aureus[J]. Benef Microbes, 2015, 6(6):879-886. doi: 10.3920/BM2015.0019 URL

实验模型 Experimental model	生物活性物质 Bioactive substance	来源 Source	作用机制 Mechanism of action	效果 Effect	参考文献 Reference
E.coli（或LPS）诱导的bMECs炎症模型	咖啡酸	植物源的多酚化合物	抑制NF-κB和MAPK信号通路的活化,显著降低TNF-α、IL-6、IL-8和IL-1β的表达	减轻bMECs的炎症反应	[11-12]
	桔梗皂苷D	桔梗根	抑制TNF-α、IL-1β和IL-6的表达,同时上调肝核受体α（LXRα）的表达以及抑制NF-κB信号通路的激活		[13-14]
	二十二碳六烯酸	海鱼油脂	抑制TNF-α、IL-1β和IL-6的产生以及NF-κB信号通路的活化。		[15]
	甲氧补骨脂素	伞形科植物	抑制IL-1β、IL-6、TNF-α和IL-8基因mRNA的表达、降低环氧合酶-2（cyclooxygenase-2,COX-2）的蛋白水平、促进高迁移率族蛋白B1（high-mobility group box 1,HMGB1）从细胞核向细胞质的转移;并显著抑制NF-κB易位和信号转导子及转录激活子（signal transducers and activators of transcription,STAT1）的磷酸化		[16]
	鱼腥草素钠	鱼腥草	抑制炎症因子TNF-α、IL-1β和IL-6的产生以及P-p65和IκBα降解,进而抑制NF-κB信号通路的活化。		[17-18]
	桑色素	桑科中草药	抑制TNF-α、IL-1β和IL-6的表达以及NF-κB和MAPK信号通路的活化		[19]
S. aureus（或LTA）诱导的bMECs炎症模型	麝香草酚	百里香和牛至	抑制NF-κB的活化,并以剂量依赖性的方式抑制S. aureus在bMECs中的内化作用,并下调气管抗菌肽（tracheal antimicrobial peptide,TAP）和β-防御素5（β-defensin 5,BNBD5）基因mRNA的表达	发挥bMECs的抗炎作用	[20-21]
S. aureus（或LTA）诱导的bMECs炎症模型	连翘酯苷A	连翘	显著下调TNF-α、IL-1β和IL-6的表达,并通过抑制P38、ERK、JNK和P-p65而干扰MAPK和NF-κB信号通路的激活。	发挥bMECs的抗炎作用	[22-23]
氨诱导的bMECs的氧化应激模型	黄芪甲苷	黄芪	胱天蛋白酶-3（caspase-3）和p53磷酸化水平显著降低,通过激活核因子红细胞2相关因子2-抗氧化反应元件信号通路（nuclear factor erythrocyte two related factors-2-antioxidant response element,Nrf2-ARE）抑制ROS的产生	降低bMECs的氧化应激,减轻细胞炎症损伤	[24-25]
氨诱导的bMECs的氧化应激模型	茶多酚	绿茶	降低ROS的产生和增强核因子红细胞2 样2（nuclear factor erythroid 2 like 2,NFE2L2）以及血红素氧化酶-1（heme oxygenase-1,HMOX1）途径	降低bMECs的氧化应激,减轻细胞炎症损伤	[26]

实验模型 Experimental model	生物活性物质 Bioactive substance	来源 Source	作用机制 Mechanism of action	效果 Effect	参考文献 Reference
E.coli（或LPS）诱导的bMECs炎症模型	咖啡酸	植物源的多酚化合物	抑制NF-κB和MAPK信号通路的活化,显著降低TNF-α、IL-6、IL-8和IL-1β的表达	减轻bMECs的炎症反应	[11-12]
	桔梗皂苷D	桔梗根	抑制TNF-α、IL-1β和IL-6的表达,同时上调肝核受体α（LXRα）的表达以及抑制NF-κB信号通路的激活		[13-14]
	二十二碳六烯酸	海鱼油脂	抑制TNF-α、IL-1β和IL-6的产生以及NF-κB信号通路的活化。		[15]
	甲氧补骨脂素	伞形科植物	抑制IL-1β、IL-6、TNF-α和IL-8基因mRNA的表达、降低环氧合酶-2（cyclooxygenase-2,COX-2）的蛋白水平、促进高迁移率族蛋白B1（high-mobility group box 1,HMGB1）从细胞核向细胞质的转移;并显著抑制NF-κB易位和信号转导子及转录激活子（signal transducers and activators of transcription,STAT1）的磷酸化		[16]
	鱼腥草素钠	鱼腥草	抑制炎症因子TNF-α、IL-1β和IL-6的产生以及P-p65和IκBα降解,进而抑制NF-κB信号通路的活化。		[17-18]
	桑色素	桑科中草药	抑制TNF-α、IL-1β和IL-6的表达以及NF-κB和MAPK信号通路的活化		[19]
S. aureus（或LTA）诱导的bMECs炎症模型	麝香草酚	百里香和牛至	抑制NF-κB的活化,并以剂量依赖性的方式抑制S. aureus在bMECs中的内化作用,并下调气管抗菌肽（tracheal antimicrobial peptide,TAP）和β-防御素5（β-defensin 5,BNBD5）基因mRNA的表达	发挥bMECs的抗炎作用	[20-21]
S. aureus（或LTA）诱导的bMECs炎症模型	连翘酯苷A	连翘	显著下调TNF-α、IL-1β和IL-6的表达,并通过抑制P38、ERK、JNK和P-p65而干扰MAPK和NF-κB信号通路的激活。	发挥bMECs的抗炎作用	[22-23]
氨诱导的bMECs的氧化应激模型	黄芪甲苷	黄芪	胱天蛋白酶-3（caspase-3）和p53磷酸化水平显著降低,通过激活核因子红细胞2相关因子2-抗氧化反应元件信号通路（nuclear factor erythrocyte two related factors-2-antioxidant response element,Nrf2-ARE）抑制ROS的产生	降低bMECs的氧化应激,减轻细胞炎症损伤	[24-25]
氨诱导的bMECs的氧化应激模型	茶多酚	绿茶	降低ROS的产生和增强核因子红细胞2 样2（nuclear factor erythroid 2 like 2,NFE2L2）以及血红素氧化酶-1（heme oxygenase-1,HMOX1）途径	降低bMECs的氧化应激,减轻细胞炎症损伤	[26]