动物营养学报    2020, Vol. 32 Issue (10): 4708-4715    PDF    
围产期奶牛糖脂代谢与健康养殖研究进展
李胜利 , 郝阳毅 , 王蔚 , 王雅晶     
中国农业大学动物科学技术学院, 动物营养学国家重点实验室, 北京市生鲜乳质量安全工程技术研究中心, 北京 100193
摘要: 围产期奶牛消化代谢病高发,已经成为制约我国奶牛健康养殖的重要因素之一。本文从围产期奶牛糖脂代谢和胃肠道健康角度进行综述,阐明围产期奶牛糖脂代谢分子机制及面临的挑战,揭示围产期奶牛胃肠道功能及其微生物区系变化的潜在规律,指明围产期奶牛营养调控方向,为我国围产期奶牛健康养殖提供理论参考。
关键词: 围产期奶牛    糖脂代谢    胃肠道    营养调控    
Research Progress on Glucose-Lipid Metabolism and Healthy Feeding in Transition Dairy Cows
LI Shengli , HAO Yangyi , WANG Wei , WANG Yajing     
Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Abstract: The high incidence of digestive and metabolic diseases in dairy cows during the transition period has become one of the important factors restricting the healthy feeding of dairy cows in China. The article reviewed the glucose-lipid metabolism and gastrointestinal health of the transition dairy cows, elaborated on the challenges and molecular mechanisms of the glucose-lipid metabolism of dairy cows during the transition period, summarized the alteration of the gastrointestinal tract function and bacteria community of dairy cows during the transition period, gave the directions of nutritional regulation and provided theoretical reference for healthy feeding of the transition dairy cows in China.
Key words: transition dairy cows    glucose-lipid metabolism    gastrointestinal tract    nutritional regulation    

围产期是奶牛整个泌乳周期中的一个重要时期,分为围产前期(产前3周)和围产后期(产后3周)。该期间奶牛要经历分娩应激、泌乳应激、饲粮结构和环境的改变等,给奶牛生理和代谢带来巨大的挑战,直接或间接地影响着奶牛的健康状况。奶牛只有平稳渡过围产期,才能为整个泌乳周期的高产奠定坚实的基础,因此,围产期奶牛的健康管理尤为重要。然而,由于干物质采食量(dry matter intake,DMI)不足和能量输出加剧,能量负平衡(negative energy balance,NEB)诱发的糖脂代谢异常是围产期奶牛面临的首要问题[1]。其临床症状主要为体脂分解加剧和胰岛素敏感性降低,进而引发脂肪肝和酮病等[2]。随着我国奶牛养殖业的迅猛发展,奶牛患营养代谢病的比例逐渐增多,围产期成为奶牛代谢病发生的密集时期。对我国100头以上规模化牧场调研数据显示,奶牛产后60 d内淘汰率占整个泌乳期的27%,其中消化和代谢病是最主要淘汰原因[3]

围产期奶牛由于饲粮组成和营养水平发生改变,消化道微生物组成和代谢也随之发生变化,表现为消化道微生物丰度降低,淀粉降解菌含量升高,但消化道优势菌种类变化较小[4]。在围产后期,由于饲粮中精料含量的突然增加,大量挥发性脂肪酸(volatile fatty acid,VFA)和乳酸在瘤胃中蓄积,极易造成奶牛亚急性瘤胃酸中毒(subacute rumen acidosis,SARA)[5-6]。SARA可降低奶牛生产性能,甚至损害奶牛机体健康[7]。为适应饲粮的变化和产后机体能量需求,奶牛的胃肠道也会在形态和功能上发生相应的改变,如瘤胃乳头在奶牛围产后期迅速发育,以适应高精料饲粮[8-9]。因此,本文拟围绕围产期奶牛糖脂代谢及胃肠道健康进行综述,结合国内外最新研究进展,指明围产期奶牛营养调控方向,为我国围产期奶牛健康养殖提供理论参考。

1 围产期奶牛糖脂代谢异常的诱发因素及其对生产性能的影响 1.1 围产期奶牛糖脂代谢异常的诱发因素

围产期奶牛由于能量输出加剧且采食量不足,极易造成NEB[1]。在NEB状态下,奶牛机体将主动进行体脂动员,通过脂肪组织释放大量非酯化脂肪酸(non-esterified fatty acids,NEFA)进入肝脏代谢,然后进行氧化供能。然而,肝脏对NEFA的代谢能力有限,使得部分NEFA在肝脏不完全氧化形成酮体,主要是β-羟基丁酸(β-hydroxybutyric acid,BHBA),不仅产能效率低,还易诱发酮病。此外,过多的NEFA会再酯化形成甘油三酯(triglyceride,TG),当TG不能及时与极低密度脂蛋白(very low density lipoprotein,VLDL)结合转运出肝脏时,将在肝脏积累导致肝脏脂肪浸润,严重时诱发脂肪肝,损害肝脏健康和免疫功能[10-11]。有研究表明,脂肪浸润干扰肝脏细胞自噬活动,引起肝脏炎症反应,进一步降低了肝脏糖异生功能[12]。甲基丙二酸单酰辅酶A变位酶(methylmalonyl-CoA mutase,MUT)是将丙酸盐转变为琥珀酸盐的重要催化酶,该过程是肝脏三羧酸循环中关键步骤。奶牛产后肝脏中MUT基因和相关糖异生基因表达量下降,进而限制奶牛能量代谢,加剧糖脂代谢异常[13]

1.2 围产期奶牛糖脂代谢异常对生产性能的影响

对美国东北部2 290头围产期奶牛进行跟踪调研发现,当奶牛产前血液NEFA含量≥0.33 mEq/L,奶牛305 d奶产量减少683 kg;当奶牛产后血液NEFA含量≥0.72 mEq/L,奶牛305 d奶产量下降647 kg;或者奶牛产后血液BHBA含量≥10 mg/dL,奶牛305 d奶产量下降393 kg。简言之,当产后奶牛血液NEFA含量≥0.72 mEq/L或者BHBA含量≥10 mg/dL,会降低奶牛生产性能[10]。由于脂肪氧化不完全在奶牛机体内形成酮体,进而引发酮病,Meta分析表明当奶牛患有亚临床型酮病,其遭受真胃移位、临床型酮病、泌乳早期淘汰或者死亡和胎衣不下的概率分别是正常奶牛的3.33、5.38、1.92和1.52倍[14]。糖脂代谢异常也会延长奶牛产后空怀时间[10]。有研究表明,糖脂代谢异常主要通过影响繁殖性能和减少奶产量给奶牛养殖带来经济损失[15]

2 围产期奶牛糖脂代谢分子机制

肝脏是奶牛最大的代谢器官之一,具有调控机体代谢的功能。通过肝脏转录组研究发现奶牛经历产犊后,其肝脏中大约有10%的基因表达量发生改变,这些基因主要与脂肪酸氧化及代谢、糖异生和胆固醇代谢有关[16]

2.1 体脂动员加剧

在NEB状态下,为满足泌乳和机体代谢的能量需求,奶牛通过自身适应性调节机制动员机体能量储备,导致体脂动员[17-18]。奶牛的体脂动员受到多种激素调控,儿茶酚胺通常为去甲肾上腺素、肾上腺素和多巴胺这3种激素的统称。研究表明,儿茶酚胺与脂肪细胞表面的β-肾上腺素受体结合,激活腺苷酸环化酶,将ATP转化为环磷酸腺苷(cAMP)。cAMP的积累会诱导蛋白激酶A活化,进而使脂滴包被蛋白磷酸化并引发脂解级联反应[19]。β-肾上腺素主要有3种类型,分别为β1、β2和β3,其中,β1和β2具有在脂肪组织中分解脂质的功能。研究表明,围产后期奶牛皮下组织中肾上腺素的活性和反应能力明显增加,进而促进脂肪分解[20]。脂肪细胞也是胰岛素反应最为敏感的细胞之一,胰岛素具有刺激葡萄糖转运和脂肪合成的作用,可以协助脂肪组织吸收游离脂肪酸,并抑制脂肪分解[21]。胰岛素可通过激活蛋白激酶B来抑制脂肪分解。产后奶牛常发生胰岛素拮抗,且蛋白激酶B在肝脏中发生磷酸化,促进脂质分解和刺激脂肪组织糖异生,即体脂动员[22-23]。奶牛体脂动员也受到生长激素、催乳素、糖皮质激素等多种激素共同调节。在NEB状态下,奶牛通过体脂动员来满足产后机体代谢和泌乳需要,但过量体脂动员也会给奶牛带来脂肪肝和酮病等一系列负面效应[24]

2.2 糖异生代谢旺盛

围产后期由于泌乳启动,奶牛需要合成大量乳糖。因此该阶段奶牛体内代谢葡萄糖严重不足,葡萄糖需要量由产前1 000~1 100 g/d剧增到2 500 g/d[25-26]。为了满足泌乳需要,围产后期奶牛将增加肝脏糖异生和减少外周组织葡萄糖氧化来调节糖代谢平衡,使更多的葡萄糖用于合成乳糖[25]。瘤胃发酵产生的丙酸为反刍动物肝脏糖异生主要底物来源,占糖异生总量的50%~60%;其次是三羧酸循环的乳酸,占糖异生总量的20%~30%;脂肪组织分解产生的甘油,占糖异生总量的2%~4%;其余为蛋白质分解代谢的氨基酸[25, 27]。围产后期奶牛饲粮中精料比例增加,瘤胃发酵产生更多丙酸,将为肝脏糖异生提供足够的底物。有研究表明,在奶牛产后的第1和21天,丙酸盐通过肝脏转化为葡萄糖的比例分别比产前第21天分别提高了19%和29%[25, 28]。乳酸可以为肝脏糖异生提供生碳源,加速碳循环进而满足奶牛葡萄糖需要。奶牛产后高能高精饲粮能够产生更多的乳酸,其对肝脏葡萄糖的贡献度从3%增加到34%[29]。奶牛糖异生途径也受多种酶活性调节,主要为葡萄糖-6-磷酸酶、丙酮酸羧化酶和磷酸烯醇式丙酮酸羧化酶[30]。此外,肾上腺素、胰岛素、胰高血糖素、生长激素和糖皮质激素等多种激素也参与糖异生的调控[30]

2.3 肝脏胆固醇代谢加剧

肝脏胆固醇的体内平衡涉及多种生化途径,例如肝脏可以自身合成胆固醇,从血液摄取胆固醇需要低密度脂蛋白(low-density lipoprotein,LDL)作为载体,将胆固醇以VLDL形式分泌到血液中,形成胆汁酸等[31]。由于泌乳的启动,奶牛肝脏中胆固醇合成、酯化、转运和胆汁酸合成相关的mRNA表达量升高,以满足牛奶的能量需要。随着泌乳天数达到3周,肝脏胆固醇代谢的相关基因表达量恢复到产前水平[32]。从基因表达水平可以看出,肝脏对产后奶牛胆固醇代谢作出积极应答,但血液中胆固醇和TG含量在产后1周达到最低,这可能与肝脏中缺乏VLDL导致胆固醇输出机制受损,同时与这些化合物向乳汁中的转移增强有关[33]。因此,需要提高围产后期奶牛肝脏转运功能,从而满足奶牛产后胆固醇代谢需要。

2.4 调控糖脂代谢新机制探索

胆汁酸是一种内分泌信号分子,可以通过激活胆汁酸受体对葡萄糖、脂肪以及能量稳态产生调节作用[34]。法尼醇受体是连接胆汁酸与葡萄糖及脂质代谢的关联分子。脂蛋白可将外围组织中的胆固醇转运到肝脏,促进胆固醇转化为胆汁酸[35]。围产期奶牛肝脏胆固醇代谢紊乱,抑制能量利用[16],法尼醇受体能够促进VLDL含量增加[36],进而将TG从肝脏中转运出去,缓解脂肪肝。以脂蛋白和法尼醇受体作为调控围产期奶牛肝脏脂质代谢及胆固醇代谢的新靶点,或可为解决围产期糖脂代谢障碍提供新思路。

3 围产期奶牛胃肠道生理变化与挑战 3.1 胃肠道菌群变化

奶牛胃肠道菌群存在一定的稳定性,在不受外界影响下,瘤胃及粪便菌群多样性和丰度维持不变[37]。围产期奶牛由于饲粮更换,胃肠道菌群稳态将被破坏,瘤胃菌群适应性较强,能够在产后第21天恢复产前多样性水平,而结肠菌群适应性相对较弱,产后第21天其菌群多样性仍未得到有效恢复[38]。奶牛瘤胃中丰度最高的2个菌门为拟杆菌门(Bacteroidetes)和厚壁菌门(Firmicutes),当由产前高粗饲粮转变为产后高精饲粮,瘤胃拟杆菌门和厚壁菌门的比例会由6:1增加到12:1[39]。同时,高精饲粮导致瘤胃丙酸产量增多,进而增加了氢离子竞争,诱发瘤胃古菌区系发生改变[40],比如产甲烷杆菌(Methanobacteriales)含量增加[41]。围产后期饲粮能量水平也影响瘤胃菌群组成,低能饲粮显著增加产后第7天瘤胃液中瘤胃球菌属(Ruminococcaceae)和产琥珀酸丝状杆菌属(Fibrobacter succinogenes)含量[42]。围产后期奶牛瘤胃菌属的改变,也与奶牛自身产奶量有关。相比于产奶量低的奶牛,高产奶牛在围产后期瘤胃中拟杆菌属(Bacteroidetes)、白色瘤胃球菌属(Ruminococcus albus)、溶纤维丁酸弧菌属(Butyrivibrio fibrisolvens)含量更高,这些菌属均与瘤胃中丙酸含量高度相关。而低产奶牛在围产后期瘤胃中含有更多毛螺菌属(Lachnospiraceae)和双歧杆菌属(Bifidobacterium)[43]。奶牛饲粮精料水平大幅度增加,还可以减少盲肠和粪便中牛链球菌属(Streptococcus bovis)含量,增加大肠杆菌(Escherichia coli)含量[44]。围产期是奶牛胃肠道菌群组成变化的重要窗口时期,更应该关注和合理调控围产期奶牛胃肠道菌群,实现胃肠道功能平稳过渡。

3.2 新产牛瘤胃酸中毒

有研究报道,大约有19%新产牛会经历SARA[7]。Baldwin等[45]研究表明,奶牛从泌乳第14天到第240天,瘤胃容积增加50%,后肠段容积增加38%。相比于瘤胃菌群迅速适应饲粮更换,瘤胃上皮发育相对滞后。由于瘤胃乳头无法迅速发育成熟,精料发酵产生大量的VFA在瘤胃中蓄积,降低瘤胃液pH,引发SARA[5-6]。SARA会导致奶牛DMI下降,乳脂率和乳脂产量降低,还可以引发全身性炎症[7]。最新研究表明,SARA可导致瘤胃内产生大量内毒素脂多糖(lipopolysaccharide,LPS),LPS通过后肠道进入机体,引起奶牛机体炎症,进而通过高密度脂蛋白和乳糜微粒增加肝脏中TG含量,抑制脂肪在肝脏中供能[46-47]。同时,LPS作为革兰氏阴性菌细胞壁组成成分,是奶牛机体内毒素和损害机体免疫系统的主要成分[48]。奶牛瘤胃中主要菌群为厚壁菌和拟杆菌[37, 40],有人用厚壁菌门/拟杆菌门(Firmicutes/Bacteroides,F/B)值对瘤胃发酵模式及生产指标进行关联分析,结果表明当奶牛由于高精料饲粮遭受SARA,瘤胃F/B值会升高,且SARA越严重,F/B值越高[44, 49],表明瘤胃菌群F/B值在一定程度上能够反映瘤胃代谢状况。SARA已经成为影响奶牛机体健康的主要胃肠道疾病之一,在围产期奶牛的饲养管理中需要格外重视。

4 围产期奶牛营养调控与胃肠道健康管理 4.1 营养添加剂在围产期奶牛上的应用

围产期奶牛要经历胎儿分娩和生理机能转变,常伴随着机体代谢异常及炎症发生,因此需要一些功能性营养添加剂为其健康提供保障。氨基酸不仅用于乳蛋白的合成,还可以用于葡萄糖合成、改善肝脏功能、缓减炎症反应和氧化应激、促进激素及酶合成等[50]。围产前期奶牛饲粮中添加过瘤胃赖氨酸和蛋氨酸,能够显著提升产后奶牛乳房健康和机体免疫[51]。莫能菌素为链霉菌所分泌的一种物质,又名“瘤胃素”。围产期奶牛饲粮添加莫能菌素,能够提高丙酸转变为葡萄糖的效率,同时减少葡萄糖在机体内被氧化,进而提升围产期奶牛能量代谢状态[52]。生物素作为糖异生限速酶的辅助因子,烟酸作为能量代谢辅酶重要前体物,均可调控糖脂代谢相关途径,促进围产期奶牛能量利用[25]。胆碱可以促进VLDL合成,加速肝脏TG转运,饲粮添加胆碱能够调控肝细胞能量和脂质代谢,减少肝脏脂肪蓄积[17]。经产围产期奶牛补饲过瘤胃胆碱能够增加奶牛的奶产量,最佳的添加量应不低于12.9 g/d[53]。此外,需注意围产期奶牛血钙水平,奶牛产后低血钙可以诱发产褥热,降低DMI和奶产量。同时,有研究表明血钙水平可以影响嗜中性粒细胞的吞噬功能,围产期的补钙策略与产后免疫力具有相关关系[54]。为保障奶牛产后处于正常血钙水平,产前饲粮可以添加一定量阴离子盐,使饲粮阴阳离子差为负值,缓解产后奶牛低血钙[55]。生产中当产后奶牛血钙水平低于1.2 mmol/L,要及时补钙。

4.2 菌群移植和饲粮营养水平调控DMI

围产期奶牛由于DMI不足导致NEB是引发一系列产后代谢疾病的根源。因此,提高围产期奶牛DMI至关重要。蒋涛[56]通过给围产后期奶牛灌服高产奶牛瘤胃液的方式重塑奶牛胃肠道菌群,结果表明菌群移植促使围产期奶牛胃肠道的菌群结构和相对成熟度更接近泌乳高峰期奶牛,显著提高新产牛的采食量和产奶量。门洪凯[57]通过对新产牛移植高产奶牛的鲜活和灭菌瘤胃液,结果发现灭活瘤胃液对采食量和产奶量的积极效应要大于鲜活瘤胃液。其内在机制仍有待阐明,但综合以上试验可以明确瘤胃液移植确实可以提升围产期奶牛采食量和产奶量。

产前合理的体况管理将有助于奶牛顺利度过围产期。韩春林[58]研究表明,围产期奶牛体况为3.25分(5分制)将有利于奶牛产犊、泌乳性能和健康。黄文明[59]研究表明,产前饲喂低能饲粮导致DMI下降,但增加了产后DMI,进而减少体脂动员,提高奶牛健康。同时,苏华维[60]研究表明,产前饲喂高能饲粮导致奶牛产后食欲恢复较慢,体重损失较多。董双钊[61]研究表明,对于蒙荷杂交泌乳牛,产前饲粮最佳能量水平为NRC[62]推荐值的84%。围产前期的健康管理将为产后高产奠定坚实基础,综上所述,我们推荐围产前期奶牛应饲喂低能饲粮,同时保证奶牛合理体况。

4.3 围产期奶牛胃肠道健康管理

健康的瘤胃内环境需要在VFA的产生和吸收之间维持动态平衡,过多的VFA将导致瘤胃液pH下降[63-64]。早在1987年就有学者认为在干奶期增加瘤胃上皮表面积,可以作为预防瘤胃中过高VFA含量和过低pH的有效策略[65]。然而近期研究表明,通过补饲精料可以增加干奶期奶牛瘤胃乳头表面积,但对产后奶牛瘤胃乳头表面积并没有影响[8]。产后奶牛迅速增加精料供给相比于缓慢增加精料补给(1.00 kg/d vs. 0.25 kg/d,直到10.90 kg/d),奶牛瘤胃乳头表面积在产后第16、30和44天显著增加[9]。但无论产前多补给精料还是改变产后精料增加节奏,均未改变瘤胃乳头吸收VFA效率[8-9]。影响瘤胃上皮对VFA的吸收效率主要有3个因素:VFA产生部位与吸收部位的平衡、瘤胃上皮的通透性和瘤胃上皮的血流速率[66-67]。关于补饲精料促进瘤胃乳头提早发育能否提升瘤胃上皮吸收VFA效率,目前仍不够明确,有待进一步研究。

酵母培养物有增加奶牛瘤胃微生物纤维分解能力、降低瘤胃中乳酸浓度和增加微生物蛋白产量等诸多优势[68]。在围产期奶牛饲粮中补饲酵母类添加剂,能够增加围产后期奶牛瘤胃液pH,缩小瘤胃液pH的波动范围,减少奶牛SARA持续时间,促进胃肠道健康[69]。饲粮淀粉水平是导致奶牛遭遇SARA的主要因素,产后低淀粉饲粮(22% vs. 28%)能够有效防止瘤胃液pH过低[68]。围产期奶牛饲粮更换,要合理控制产后饲粮精料含量和粗饲料长度,保证奶牛能够充分反刍,以维持瘤胃液pH稳定[70]。相比于头胎牛,经产牛的瘤胃乳头更加发达,瘤胃功能更加健全,对精料的耐受性更强,因此要注意将头胎和经产围产期奶牛分群饲养,使用差异化饲粮[71]。此外,增加新产牛的饲喂次数,也能够有效降低其患SARA的风险[72]

5 小结

围产期是奶牛养殖中最为关键的时期,平稳过渡围产期才能为奶牛的健康和高产提供保障。由于奶牛在围产期经历NEB,引发糖脂代谢异常,甚至出现酮病,进而影响奶牛泌乳性能、繁殖性能和健康。同时,围产期奶牛由于饲粮和生理状态的改变,胃肠道也要经历微生物重塑和二次发育,因此要对围产期奶牛胃肠道健康格外关注。合理的饲粮营养水平保证奶牛采食量稳定,注重产前奶牛体况管理和营养性添加剂应用,合理分群和饲养,从而做到奶牛围产期平稳过渡。

参考文献
[1]
INGVARTSEN K L, ANDERSEN J B. Integration of metabolism and intake regulation:a review focusing on periparturient animals[J]. Journal of Dairy Science, 2000, 83(7): 1573-1597. DOI:10.3168/jds.S0022-0302(00)75029-6
[2]
MCFADDEN J W. Review:lipid biology in the periparturient dairy cow:contemporary perspectives[J]. Animal, 2020, 14(S1): s165-s175. DOI:10.1017/S1751731119003185
[3]
马佳莹.中国百头以上牧场成母牛长寿性及主要淘汰原因的调查分析[D].硕士学位论文.北京: 中国农业大学, 2016: 41.
[4]
LIMA F S, OIKONOMOU G, LIMA S F, et al. Prepartum and postpartum rumen fluid microbiomes:characterization and correlation with production traits in dairy cows[J]. Applied and Environmental Microbiology, 2015, 81(4): 1327-1337. DOI:10.1128/AEM.03138-14
[5]
PENNER G B, STEELE M A, ASCHENBACH J R, et al. Ruminant nutrition symposium:molecular adaptation of ruminal epithelia to highly fermentable diets[J]. Journal of Animal Science, 2011, 89(4): 1108-1119. DOI:10.2527/jas.2010-3378
[6]
STEELE M A, PENNER G B, CHAUCHEYRAS-DURAND F, et al. Development and physiology of the rumen and the lower gut:targets for improving gut health[J]. Journal of Dairy Science, 2016, 99(6): 4955-4966. DOI:10.3168/jds.2015-10351
[7]
PLAIZIER J C, KRAUSE D O, GOZHO G N, et al. Subacute ruminal acidosis in dairy cows:the physiological causes, incidence and consequences[J]. The Veterinary Journal, 2008, 176(1): 21-31. DOI:10.1016/j.tvjl.2007.12.016
[8]
DIEHO K, DIJKSTRA J, KLOP G, et al. The effect of supplemental concentrate fed during the dry period on morphological and functional aspects of rumen adaptation in dairy cattle during the dry period and early lactation[J]. Journal of Dairy Science, 2017, 100(1): 343-356. DOI:10.3168/jds.2016-11575
[9]
DIEHO K, DIJKSTRA J, SCHONEWILLE J T, et al. Changes in ruminal volatile fatty acid production and absorption rate during the dry period and early lactation as affected by rate of increase of concentrate allowance[J]. Journal of Dairy Science, 2016, 99(7): 5370-5384. DOI:10.3168/jds.2015-10819
[10]
OSPINA P A, NYDAM D V, STOKOL T, et al. Associations of elevated nonesterified fatty acids and β-hydroxybutyrate concentrations with early lactation reproductive performance and milk production in transition dairy cattle in the northeastern United States[J]. Journal of Dairy Science, 2010, 93(4): 1596-1603. DOI:10.3168/jds.2009-2852
[11]
WEBER C, HAMETNER C, TUCHSCHERER A, et al. Hepatic gene expression involved in glucose and lipid metabolism in transition cows:effects of fat mobilization during early lactation in relation to milk performance and metabolic changes[J]. Journal of Dairy Science, 2013, 96(9): 5670-5681. DOI:10.3168/jds.2012-6277
[12]
DU X L, LIU G W, LOOR J J, et al. Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function[J]. Journal of Dairy Science, 2018, 101(12): 11175-11185. DOI:10.3168/jds.2018-15120
[13]
LAGUNA J G, CARDOSO M S, LIMA J A, et al. Expression of hepatic genes related to energy metabolism during the transition period of Holstein and F1 Holstein-Gir cows[J]. Journal of Dairy Science, 2017, 100(12): 9861-9870. DOI:10.3168/jds.2016-12459
[14]
RABOISSON D, MOUNIÉ M, MAIGNÉ E. Diseases, reproductive performance, and changes in milk production associated with subclinical ketosis in dairy cows:a Meta-analysis and review[J]. Journal of Dairy Science, 2014, 97(12): 7547-7563. DOI:10.3168/jds.2014-8237
[15]
BENEDET A, MANUELIAN C L, ZIDI A, et al. Invited review:β-hydroxybutyrate concentration in blood and milk and its associations with cow performance[J]. Animal, 2019, 13(8): 1676-1689. DOI:10.1017/S175173111900034X
[16]
HA N T, DRÖGEMÜLLER C, REIMER C, et al. Liver transcriptome analysis reveals important factors involved in the metabolic adaptation of the transition cow[J]. Journal of Dairy Science, 2017, 100(11): 9311-9323. DOI:10.3168/jds.2016-12454
[17]
孙菲菲.胆碱和蛋氨酸对奶牛围产期营养平衡和机体健康的影响及机制[D].博士学位论文.杨凌: 西北农林科技大学, 2017: 144-145. http://cdmd.cnki.com.cn/Article/CDMD-10712-1017101932.htm
[18]
王艳明.日粮脂肪和能量水平对奶牛氧化应激、生产性能的影响及抗氧化剂添加效果研究[D].博士学位论文.杭州: 浙江大学, 2010: 93-95. http://d.wanfangdata.com.cn/Thesis/Y1713834
[19]
DUNCAN R E, AHMADIAN M, JAWORSKI K, et al. Regulation of lipolysis in adipocytes[J]. Annual Review of Nutrition, 2007, 27: 79-101. DOI:10.1146/annurev.nutr.27.061406.093734
[20]
JASTER E H, WEGNER T N. Beta-adrenergic receptor involvement in lipolysis of dairy cattle subcutaneous adipose tissue during dry and lactating state[J]. Journal of Dairy Science, 1981, 64(8): 1655-1663. DOI:10.3168/jds.S0022-0302(81)82743-9
[21]
KAHN S E, PRIGEON R L, SCHWARTZ R S, et al. Obesity, body fat distribution, insulin sensitivity and islet β-cell function as explanations for metabolic diversity[J]. The Journal of Nutrition, 2001, 131(2): 354S-360S. DOI:10.1093/jn/131.2.354S
[22]
DE KOSTER J D, OPSOMER G. Insulin resistance in dairy cows[J]. Veterinary Clinics of North America:Food Animal Practice, 2013, 29(2): 299-322. DOI:10.1016/j.cvfa.2013.04.002
[23]
ZACHUT M, HONIG H, STRIEM S, et al. Periparturient dairy cows do not exhibit hepatic insulin resistance, yet adipose-specific insulin resistance occurs in cows prone to high weight loss[J]. Journal of Dairy Science, 2013, 96(9): 5656-5669. DOI:10.3168/jds.2012-6142
[24]
CONTRERAS G A, STRIEDER-BARBOZA C, RAPHAEL W. Adipose tissue lipolysis and remodeling during the transition period of dairy cows[J]. Journal of Animal Science and Biotechnology, 2017, 8(1): 41.
[25]
魏筱诗.烟酰胺对围产期奶畜糖脂代谢及其子代肠道发育的影响和机制[D].博士学位论文.杨凌: 西北农林科技大学, 2019: 4-8. http://cdmd.cnki.com.cn/Article/CDMD-10712-1019844582.htm
[26]
DRACKLEY J K, OVERTON T R, DOUGLAS G N. Adaptations of glucose and long-chain fatty acid metabolism in liver of dairy cows during the periparturient period[J]. Journal of Dairy Science, 2001, 84(Suppl.1): E100-E112.
[27]
REYNOLDS C K, AIKMAN P C, LUPOLI B, et al. Splanchnic metabolism of dairy cows during the transition from late gestation through early lactation[J]. Journal of Dairy Science, 2003, 86(4): 1201-1217. DOI:10.3168/jds.S0022-0302(03)73704-7
[28]
HUHTANEN P, VANHATALO A, VARVIKKO T. Effects of abomasal infusions of histidine, glucose, and leucine on milk production and plasma metabolites of dairy cows fed grass silage diets[J]. Journal of Dairy Science, 2002, 85(1): 204-216. DOI:10.3168/jds.S0022-0302(02)74069-1
[29]
LARSEN M, KRISTENSEN N B. Precursors for liver gluconeogenesis in periparturient dairy cows[J]. Animal, 2013, 7(10): 1640-1650. DOI:10.1017/S1751731113001171
[30]
JITRAPAKDEE S. Transcription factors and coactivators controlling nutrient and hormonal regulation of hepatic gluconeogenesis[J]. The International Journal of Biochemistry & Cell Biology, 2012, 44(1): 33-45.
[31]
CHANG T Y, CHANG C C Y, OHGAMI N, et al. Cholesterol sensing, trafficking, and esterification[J]. Annual Review of Cell and Developmental Biology, 2006, 22: 129-157. DOI:10.1146/annurev.cellbio.22.010305.104656
[32]
SCHLEGEL G, RINGSEIS R, KELLER J, et al. Changes in the expression of hepatic genes involved in cholesterol homeostasis in dairy cows in the transition period and at different stages of lactation[J]. Journal of Dairy Science, 2012, 95(7): 3826-3836. DOI:10.3168/jds.2011-5221
[33]
KESSLER E C, GROSS J J, BRUCKMAIER R M, et al. Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation[J]. Journal of Dairy Science, 2014, 97(9): 5481-5490. DOI:10.3168/jds.2014-7926
[34]
MOLINARO A, WAHLSTRÖM A, MARSCHALL H U. Role of bile acids in metabolic control[J]. Trends in Endocrinology & Metabolism, 2018, 29(1): 31-41.
[35]
SINAL C J, TOHKIN M, MIYATA M, et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis[J]. Cell, 2000, 102(6): 731-744. DOI:10.1016/S0092-8674(00)00062-3
[36]
CLAUDEL T, STAELS B, KUIPERS F. The farnesoid X receptor[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005, 25(10): 2020-2030. DOI:10.1161/01.ATV.0000178994.21828.a7
[37]
HUANG S, JI S K, YAN H, et al. The day-to-day stability of the ruminal and fecal microbiota in lactating dairy cows[J]. MicrobiologyOpen, 2020, 9(5): e990.
[38]
BACH A, LÓPEZ-GARCÍA A, GONZÁLEZ-RECIO O, et al. Changes in the rumen and colon microbiota and effects of live yeast dietary supplementation during the transition from the dry period to lactation of dairy cows[J]. Journal of Dairy Science, 2019, 102(7): 6180-6198. DOI:10.3168/jds.2018-16105
[39]
PITTA D W, KUMAR S, VECCHIARELLI B, et al. Temporal dynamics in the ruminal microbiome of dairy cows during the transition period[J]. Journal of Animal Science, 2014, 92(9): 4014-4022. DOI:10.2527/jas.2014-7621
[40]
ZHU Z G, KRISTENSEN L, DIFFORD G F, et al. Changes in rumen bacterial and archaeal communities over the transition period in primiparous Holstein dairy cows[J]. Journal of Dairy Science, 2018, 101(11): 9847-9862. DOI:10.3168/jds.2017-14366
[41]
ZHU Z G, NOEL S J, DIFFORD G F, et al. Community structure of the metabolically active rumen bacterial and archaeal communities of dairy cows over the transition period[J]. PLoS One, 2017, 12(11): e0187858. DOI:10.1371/journal.pone.0187858
[42]
HUANG W M, WANG L B, LI S L, et al. Effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in Holstein cows[J]. Asian-Australasian Journal of Animal Sciences (AJAS), 2019, 32(5): 648-656. DOI:10.5713/ajas.18.0624
[43]
SOFYAN A, UYENO Y, SHINKAI T, et al. Metagenomic profiles of the rumen microbiota during the transition period in low-yield and high-yield dairy cows[J]. Animal Science Journal, 2019, 90(10): 1362-1376. DOI:10.1111/asj.13277
[44]
PLAIZIER J C, LI S C, TUN H M, et al. Nutritional models of experimentally-induced subacute ruminal acidosis (SARA) differ in their impact on rumen and hindgut bacterial communities in dairy cows[J]. Frontiers in Microbiology, 2016, 7: 2128.
[45]
BALDWIN VI R L, MCLEOD K R, CAPUCO A V. Visceral tissue growth and proliferation during the bovine lactation cycle[J]. Journal of Dairy Science, 2004, 87(9): 2977-2986. DOI:10.3168/jds.S0022-0302(04)73429-3
[46]
LI S, KHAFIPOUR E, KRAUSE D O, et al. Effects of subacute ruminal acidosis challenges on fermentation and endotoxins in the rumen and hindgut of dairy cows[J]. Journal of Dairy Science, 2012, 95(1): 294-303. DOI:10.3168/jds.2011-4447
[47]
KHIAOSA-ARD R, ZEBELI Q. Diet-induced inflammation:from gut to metabolic organs and the consequences for the health and longevity of ruminants[J]. Research in Veterinary Science, 2018, 120: 17-27. DOI:10.1016/j.rvsc.2018.08.005
[48]
KHAFIPOUR E, LI S C, PLAIZIER J C, et al. Rumen microbiome composition determined using two nutritional models of subacute ruminal acidosis[J]. Applied and Environmental Microbiology, 2009, 75(22): 7115-7124. DOI:10.1128/AEM.00739-09
[49]
MAO S Y, ZHANG R Y, WANG D S, et al. Impact of Subacute Ruminal Acidosis (SARA) adaptation on rumen microbiota in dairy cattle using pyrosequencing[J]. Anaerobe, 2013, 24: 12-19. DOI:10.1016/j.anaerobe.2013.08.003
[50]
SCHWAB C G, BRODERICK G A. A 100-year review:protein and amino acid nutrition in dairy cows[J]. Journal of Dairy Science, 2017, 100(12): 10094-10112. DOI:10.3168/jds.2017-13320
[51]
LEE C, LOBOS N E, WEISS W P. Effects of supplementing rumen-protected lysine and methionine during prepartum and postpartum periods on performance of dairy cows[J]. Journal of Dairy Science, 2019, 102(12): 11026-11039. DOI:10.3168/jds.2019-17125
[52]
MARKANTONATOS X, VARGA G A. Effects of monensin on glucose metabolism in transition dairy cows[J]. Journal of Dairy Science, 2017, 100(11): 9020-9035. DOI:10.3168/jds.2016-12007
[53]
ARSHAD U, ZENOBI M G, STAPLES C R, et al. Meta-analysis of the effects of supplemental rumen-protected choline during the transition period on performance and health of parous dairy cows[J]. Journal of Dairy Science, 2020, 103(1): 282-300. DOI:10.3168/jds.2019-16842
[54]
何雅琴.围产后期奶牛血钙浓度对外周血嗜中性粒细胞吞噬功能及相关基因表达的影响[D].硕士学位论文.北京: 中国农业大学, 2019: 30.
[55]
王铂.奶牛产前饲喂DCAD日粮对产乳热和生产性能的影响[D].硕士学位论文.北京: 中国农业大学, 2015: 26.
[56]
蒋涛.瘤胃微生物重塑对围产后期奶牛采食量和采食行为的影响[D].博士学位论文.北京: 中国农业大学, 2018: 101. http://kns.cnki.net/KCMS/detail/detail.aspx?dbcode=CDFD&dbname=CDFD&filename=1018069199.nh
[57]
门洪凯.瘤胃液移植对围产后期奶牛采食行为、反刍行为及产奶量的影响研究[D].硕士学位论文.北京: 中国农业大学, 2019: 30.
[58]
韩春林.荷斯坦奶牛围产期最佳体况及过渡天数研究[D].硕士学位论文.北京: 中国农业大学, 2017: 37.
[59]
黄文明.围产前期日粮能量水平对奶牛能量代谢和瘤胃适应性影响的研究[D].博士学位论文.北京: 中国农业大学, 2014: 60-61. http://cdmd.cnki.com.cn/Article/CDMD-10019-1014225963.htm
[60]
苏华维.中国荷斯坦奶牛围产期能量平衡及其调控研究[D].博士学位论文.北京: 中国农业大学, 2011: 93-94.
[61]
董双钊.围产前期日粮精料水平对蒙荷杂交牛能量代谢和瘤胃适应性的影响[D].硕士学位论文.北京: 中国农业大学, 2016: 57.
[62]
NRC. Nutrient requirements of dairy cattle[M]. 7th ed. Washington, D.C.: National Academy Press, 2001.
[63]
ASCHENBACH J R, PENNER G B, STUMPFF F, et al. Ruminant nutrition symposium:role of fermentation acid absorption in the regulation of ruminal pH[J]. Journal of Animal Science, 2011, 89(4): 1092-1107. DOI:10.2527/jas.2010-3301
[64]
DIJKSTRA J, ELLIS J L, KEBREAB E, et al. Ruminal pH regulation and nutritional consequences of low pH[J]. Animal Feed Science and Technology, 2012, 172(1/2): 22-33.
[65]
LIEBICH H G, DIRKSEN G, ARBEL A, et al. Fütterungsabhängige veränderungen der pansenschleimhaut von hochleistungskühen im zeitraum von der trockenstellung bis acht wochen post partum[J]. Journal of Veterinary Medicine, 1987, 34(1/2/3/4/5/6/7/8/9/10): 661-672.
[66]
STORM A C, KRISTENSEN N B. Effects of particle size and dry matter content of a total mixed ration on intraruminal equilibration and net portal flux of volatile fatty acids in lactating dairy cows[J]. Journal of Dairy Science, 2010, 93(9): 4223-4238. DOI:10.3168/jds.2009-3002
[67]
STORM A C, KRISTENSEN N B. Erratum to "Effects of particle size and dry matter content of a total mixed ration on intraruminal equilibration and net portal flux of volatile fatty acids in lactating dairy cows"[J]. Journal of Dairy Science, 2011, 94(1): 532-535. DOI:10.3168/jds.2011-94-1-532
[68]
HRISTOV A N, VARGA G, CASSIDY T, et al. Effect of Saccharomyces cerevisiae fermentation product on ruminal fermentation and nutrient utilization in dairy cows[J]. Journal of Dairy Science, 2010, 93(2): 682-692. DOI:10.3168/jds.2009-2379
[69]
SHI W, KNOBLOCK C E, YOON I, et al. Effects of supplementing a Saccharomyces cerevisiae fermentation product during the transition period on rumen fermentation of dairy cows fed fresh diets differing in starch content[J]. Journal of Dairy Science, 2019, 102(11): 9943-9955. DOI:10.3168/jds.2019-16671
[70]
HUMER E, PETRI R M, ASCHENBACH J R, et al. Invited review:practical feeding management recommendations to mitigate the risk of subacute ruminal acidosis in dairy cattle[J]. Journal of Dairy Science, 2018, 101(2): 872-888. DOI:10.3168/jds.2017-13191
[71]
KRAUSE K M, OETZEL G R. Understanding and preventing subacute ruminal acidosis in dairy herds:a review[J]. Animal Feed Science and Technology, 2006, 126(3/4): 215-236.
[72]
MACMILLAN K, GAO X, OBA M. Increased feeding frequency increased milk fat yield and may reduce the severity of subacute ruminal acidosis in higher-risk cows[J]. Journal of Dairy Science, 2017, 100(2): 1045-1054. DOI:10.3168/jds.2016-11337