断奶应激影响犊牛免疫功能的Meta分析
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摘要
本研究利用Meta分析评估断奶应激对犊牛免疫功能的影响。筛选后共纳入11篇文献,通过回归分析解释异质性来源,通过敏感性分析评估结果稳定性,使用漏斗图评估发表偏倚。Meta分析结果表明断奶应激可导致犊牛血液中中性粒细胞数量在断奶后1～3 d显著升高(P<0.001),淋巴细胞数量在断奶后1～3 d显著降低(P<0.001),单核细胞数量在断奶后11～14 d显著降低(P=0.015)。断奶应激可导致断奶后1～3 d(P=0.046)和11～14 d(P=0.001)犊牛血液中皮质醇浓度显著升高,但对断奶后5～8 d血液中皮质醇浓度无显著影响(P>0.05)。犊牛血液中触珠蛋白(P<0.001)和纤维蛋白原(P<0.001)浓度在断奶后显著升高,并持续到断奶后14 d。敏感性分析表明所有结果稳定可靠,漏斗图分析表明皮质醇、触珠蛋白和纤维蛋白原浓度存在少量的发表偏倚。本研究利用Meta分析发现犊牛血液中触珠蛋白和纤维蛋白原浓度在犊牛断奶后2周仍高于断奶前水平,可以考虑将其作为潜在应激标志物应用于今后反刍动物应激反应的研究中;同时,本研究为犊牛的健康管理和疾病预防,以及犊牛断奶应激和免疫功能相关的研究提供了科学依据。
In this study,the Meta-analysis was used to evaluate the effects of weaning stress on immunity of calves.A total of 11 articles were chosen after screening.The regression analysis was used to explain the source of heterogeneity,sensitivity analysis was used to assess the stability of results,and funnel plots were used to evaluate the publication bias.The Meta-analysis results showed that weaning stress could cause the blood neutrophil number significantly increased at 1 to 3 d post weaning(P<0.001),the lymphocyte number significantly decreased at 1 to 3 d post weaning(P< 0.001),and the monocytes number significantly decreased at 11 to14 d post weaning(P=0.015).Weaning stress could cause the blood cortisol concentration significantly elevated at both 1 to 3 d(P=0.046) and 11 to 14 d post weaning(P=0.001),while had no significant effect at5 to 8 d post weaning(P>0.05).Blood haptoglobin(P<0.001) and fibrinogen concentrations(P<0.001)were significantly increased since weaning and prolong until 14 days after weaning.Sensitivity analysis showed that all the results were stable and reliable.Funnel plot analysis revealed a small amount of publication bias in cortisol,haptoglobin and fibrinogen concentrations.This Meta-analysis found that blood haptoglobin and fibrinogen concentrations of calves were still higher than pre-weaning levels for 2 weeks after weaning,it can be considered as a potential stress marker for the future study of ruminant stress response.Meanwhile,this study provides a scientific basis for calf health management,disease prevention,and relevant studies on weaning stress and immune function in calves.
In this study,the Meta-analysis was used to evaluate the effects of weaning stress on immunity of calves.A total of 11 articles were chosen after screening.The regression analysis was used to explain the source of heterogeneity,sensitivity analysis was used to assess the stability of results,and funnel plots were used to evaluate the publication bias.The Meta-analysis results showed that weaning stress could cause the blood neutrophil number significantly increased at 1 to 3 d post weaning(P<0.001),the lymphocyte number significantly decreased at 1 to 3 d post weaning(P< 0.001),and the monocytes number significantly decreased at 11 to14 d post weaning(P=0.015).Weaning stress could cause the blood cortisol concentration significantly elevated at both 1 to 3 d(P=0.046) and 11 to 14 d post weaning(P=0.001),while had no significant effect at5 to 8 d post weaning(P>0.05).Blood haptoglobin(P<0.001) and fibrinogen concentrations(P<0.001)were significantly increased since weaning and prolong until 14 days after weaning.Sensitivity analysis showed that all the results were stable and reliable.Funnel plot analysis revealed a small amount of publication bias in cortisol,haptoglobin and fibrinogen concentrations.This Meta-analysis found that blood haptoglobin and fibrinogen concentrations of calves were still higher than pre-weaning levels for 2 weeks after weaning,it can be considered as a potential stress marker for the future study of ruminant stress response.Meanwhile,this study provides a scientific basis for calf health management,disease prevention,and relevant studies on weaning stress and immune function in calves.
引文
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[12]JOHNSTON D,KENNY D A,KELLY A K,et al.Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning[J].Animal,2016,10(9):1547-1556.
[13]张千,李发弟,李飞.断奶应激对幼龄反刍动物免疫系统的影响及其机理[J].动物营养学报,2016,28(7):1988-1997.
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[18]O'LOUGHLIN A,LYNN D J,MCGEE M,et al.Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology[J].BMC Genomics,2012,13:250.
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[20]董书伟,张世栋,王东升,等.中药治疗牛子宫内膜炎的系统评价和Meta分析[J].畜牧兽医学报,2015,46(11):2085-2096.
[21]张千,李发弟,李飞.反刍动物应激反应中糖皮质激素对免疫系统的调节机理[J].畜牧兽医学报,2017,48(5):785-792.
[22]GLASER R,KIECOLT-GLASER J K.Stress-induced immune dysfunction:implications for health[J].Nature Review s Immunology,2005,5(3):243-251.
[23]RIVIER C,VALE W.Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo[J].Endocrinology,1983,113(3):939-942.
[24]WATABE T,TANAKA K,KUMAGAE M,et al.Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man[J].The Journal of Clinical Endocrinology&Metabolism,1988,66(6):1132-1137.
[25]EVANS R M.The steroid and thyroid hormone receptor superfamily[J].Science,1988,240(4854):889-895.
[26]ZAHOREC R.Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill[J].Bratislavske Lekarske Listy,2001,102(1):5-14.
[27]TEMPELMAN R J,SAAMA P M,FREEMAN A E,et al.Genetic variation in bovine neutrophil sensitivity to glucocorticoid challenge[J].Acta Agriculturae Scandinavica,Section A:Animal Science,2002,52(4):189-202.
[28]RODRIGUES-MASCARENHAS S,DOS SANTOS N F,RUMJANEK V M.Synergistic effect between ouabain and glucocorticoids for the induction of thymic atrophy[J].Bioscience Reports,2006,26(2):159-169.
[29]DHABHAR F S.A hassle a day may keep the pathogens away:the fight-or-flight stress response and the augmentation of immune function[J].Integrative and Comparative Biology,2009,49(3):215-236.
[30]GODSON D L,BACA-ESTRADA ME,VAN KESSEL A G,et al.Regulation of bovine acute phase responses by recombinant interleukin-1 beta[J].Canadian Journal of Veterinary Research,1995,59(4):249-255.
[31]CARROLL J A,FORSBERG N E.Influence of stress and nutrition on cattle immunity[J].Veterinary Clinics of North America:Food Animal Practice,2007,23(1):105-149.
[32]ARTHINGTON J D,EICHERT S D,KUNKLE W E,et al.Effect of transportation and commingling on the acute-phase protein response,grow th,and feed intake of new ly weaned beef calves[J].Journal of Animal Science,2003,81(5):1120-1125.
[33]HORADAGODA N U,KNOX K MG,GIBBS H A,et al.Acute phase proteins in cattle:discrimination between acute and chronic inflammation[J].Veterinary Record,1999,144(16):437-441.
[2]JASPER J,WEARY D M.Effects of ad libitum milk intake on dairy calves[J].Journal of Dairy Science,2002,85(11):3054-3058.
[3]TERRM,DEVANT M,BACH A.Effect of level of milk replacer fed to Holstein calves on performance during the preweaning period and starter digestibility at weaning[J].Livestock Science,2007,110(1/2):82-88.
[4]CALLAN R J,GARRY F B.Biosecurity and bovine respiratory disease[J].Veterinary Clinics of North America:Food Animal Practice,2002,18(1):57-77.
[5]DUFF G C,GALYEAN ML.Board-invited review:recent advances in management of highly stressed,new ly received feedlot cattle[J].Journal of Animal Science,2007,85(3):823-840.
[6]SNOWDER G.GENETICS,environment and bovine respiratory disease[J].Animal Health Research Review s,2009,10(2):117-119.
[7]HULBERT L E,COBB C J,CARROLL J A,et al.The effects of early weaning on innate immune responses of Holstein calves[J].Journal of Dairy Science,2011,94(5):2545-2556.
[8]HICKEY MC,DRENNAN M,EARLEY B.The effect of abrupt weaning of suckler calves on the plasma concentrations of cortisol,catecholamines,leukocytes,acute-phase proteins and in vitro interferon-gamma production[J].Journal of Animal Science,2003,81(11):2847-2855.
[9]LYNCH E M,EARLEY B,MCGEE M,et al.Effect of abrupt weaning at housing on leukocyte distribution,functional activity of neutrophils,and acute phase protein response of beef calves[J].BMC Veterinary Research,2010,6:39.
[10]O'LOUGHLIN A,MCGEE M,WATERS S M,et al.Examination of the bovine leukocyte environment using immunogenetic biomarkers to assess immunocompetence following exposure to weaning stress[J].BMC Veterinary Research,2011,7:45.
[11]O'LOUGHLIN A,MCGEE M,DOYLE S,et al.Biomarker responses to weaning stress in beef calves[J].Research in Veterinary Science,2014,97(2):458-463.
[12]JOHNSTON D,KENNY D A,KELLY A K,et al.Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning[J].Animal,2016,10(9):1547-1556.
[13]张千,李发弟,李飞.断奶应激对幼龄反刍动物免疫系统的影响及其机理[J].动物营养学报,2016,28(7):1988-1997.
[14]LYNCH E M,EARLEY B,MCGEE M,et al.Characterisation of physiological and immunological responses in beef cow s to abrupt weaning and subsequent housing[J].BMC Veterinary Research,2010,6:37.
[15]KIMMH,YANG J Y,UPADHAYA S D,et al.The stress of weaning influences serum levels of acutephase proteins,iron-binding proteins,inflammatory cytokines,cortisol,and leukocyte subsets in Holstein calves[J].Journal of Veterinary Science,2011,12(2):151-157.
[16]LYNCH E M,MCGEE M,DOYLE S,et al.Effect of post-weaning management practices on physiological and immunological responses of weaned beef calves[J].Irish Journal of Agricultural and Food Research,2011,50(2):161-174.
[17]LYNCH E M,MCGEE M,DOYLE S,et al.Effect of pre-weaning concentrate supplementation on peripheral distribution of leukocytes,functional activity of neutrophils,acute phase protein and behavioural responses of abruptly weaned and housed beef calves[J].BMC Veterinary Research,2012,8:1.
[18]O'LOUGHLIN A,LYNN D J,MCGEE M,et al.Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology[J].BMC Genomics,2012,13:250.
[19]CHALMERS T C.The importance of properly executed Meta-analyses in the interpretation of clinical-trials[J].Acta Pharmacol Tox,1986,59:19.
[20]董书伟,张世栋,王东升,等.中药治疗牛子宫内膜炎的系统评价和Meta分析[J].畜牧兽医学报,2015,46(11):2085-2096.
[21]张千,李发弟,李飞.反刍动物应激反应中糖皮质激素对免疫系统的调节机理[J].畜牧兽医学报,2017,48(5):785-792.
[22]GLASER R,KIECOLT-GLASER J K.Stress-induced immune dysfunction:implications for health[J].Nature Review s Immunology,2005,5(3):243-251.
[23]RIVIER C,VALE W.Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo[J].Endocrinology,1983,113(3):939-942.
[24]WATABE T,TANAKA K,KUMAGAE M,et al.Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man[J].The Journal of Clinical Endocrinology&Metabolism,1988,66(6):1132-1137.
[25]EVANS R M.The steroid and thyroid hormone receptor superfamily[J].Science,1988,240(4854):889-895.
[26]ZAHOREC R.Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill[J].Bratislavske Lekarske Listy,2001,102(1):5-14.
[27]TEMPELMAN R J,SAAMA P M,FREEMAN A E,et al.Genetic variation in bovine neutrophil sensitivity to glucocorticoid challenge[J].Acta Agriculturae Scandinavica,Section A:Animal Science,2002,52(4):189-202.
[28]RODRIGUES-MASCARENHAS S,DOS SANTOS N F,RUMJANEK V M.Synergistic effect between ouabain and glucocorticoids for the induction of thymic atrophy[J].Bioscience Reports,2006,26(2):159-169.
[29]DHABHAR F S.A hassle a day may keep the pathogens away:the fight-or-flight stress response and the augmentation of immune function[J].Integrative and Comparative Biology,2009,49(3):215-236.
[30]GODSON D L,BACA-ESTRADA ME,VAN KESSEL A G,et al.Regulation of bovine acute phase responses by recombinant interleukin-1 beta[J].Canadian Journal of Veterinary Research,1995,59(4):249-255.
[31]CARROLL J A,FORSBERG N E.Influence of stress and nutrition on cattle immunity[J].Veterinary Clinics of North America:Food Animal Practice,2007,23(1):105-149.
[32]ARTHINGTON J D,EICHERT S D,KUNKLE W E,et al.Effect of transportation and commingling on the acute-phase protein response,grow th,and feed intake of new ly weaned beef calves[J].Journal of Animal Science,2003,81(5):1120-1125.
[33]HORADAGODA N U,KNOX K MG,GIBBS H A,et al.Acute phase proteins in cattle:discrimination between acute and chronic inflammation[J].Veterinary Record,1999,144(16):437-441.