2. 中国农业科学院北京畜牧兽医研究所, 动物营养学国家重点实验室, 北京 100193;
3. 中国农业科学院与世界农用林业中心农用林业与 可持续畜牧业联合实验室, 北京 100193;
4. 东北农业大学食品安全与 营养协同创新中心, 哈尔滨 150030
2. State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
3. CAAS-ICRAF Joint Laboratory on Agroforestry and Sustainable Animal Husbandry, Beijing 100193, China;
4. Synergetic Innovation Center of Food Safety and Nutrition, Harbin 150030, China
随着全球气候变暖，热应激对畜牧业的影响越来越严重。而我国幅员辽阔，每年夏季大片区域受热应激影响，导致畜禽代谢紊乱、生产性能和繁殖性能降低，造成严重的经济损失[1, 2]。热应激反应是动物机体一种自我保护机制，相关基因和蛋白质表达发生改变。而miRNAs作为一种转录后水平的调控因子，在哺乳动物基因的转录水平中只有1%~5%被编码，却调控超过60%的基因[3, 4, 5]。越来越多研究结果表明，miRNAs在畜禽抵御热应激方面发挥重要作用，如调控热休克蛋白(HSP)、氧化还原基因、免疫基因、细胞凋亡基因和相关代谢基因等[6, 7]。本文旨在对近些年热应激条件下相关miRNAs的研究进行综述，以期为畜禽热应激研究提供帮助。
1 miRNAs形成的分子机制miRNAs作为一种转录后水平调控的非编码RNA，对动物机体调控起到重要作用[8]。通过线虫胚胎发育时间控制缺陷型遗传筛选试验发现最早miRNAs家族成员lin-4[9, 10]，从此miRNAs受到广泛关注。成熟miRNAs形成过程包含以下几个步骤：miRNAs基因转录后形成长链的原miRNA(pri-miRNA)，pri-miRNA经Doarsha酶切，形成前体miRNA(pre-miRNA)，由Exportin-5蛋白质转运至细胞质，经Dicer酶切而形成成熟miRNAs[11]。miRNAs通过复合物RNA诱导沉默复合体(RISC)调控基因的表达：mRNA剪切和翻译抑制[12, 13]。在这个过程中，miRNAs可能有多个靶基因，靶基因也可能受多个miRNAs调控[14]。
2 miRNAs对热应激畜禽调控的分子机制 2.1 对热应激细胞生长和凋亡的调控细胞暴露在高温环境会受到损伤，细胞内DNA、RNA和蛋白质被抑制[15]。体外培养的细胞在热应激条件下生长停滞，并诱发其凋亡[16]。热应激诱导奶牛乳腺上皮细胞，先是热应答、DNA修复和蛋白质修复有关基因上调，之后凋亡相关基因上调[17]。miRNAs作为单链非编码小分子，调控细胞增殖、分化和凋亡[8]。miR-17-5p作用于自噬相关基因(ULK1)，抑制细胞自噬的发生[18]。miR-71直接作用于pdk-1和cdc-25.1，影响DNA损伤修复信号通路[19]。Wilmink等[20]观察高温诱导表皮成纤维细胞应激反应时发现，有83个miRNAs表达量下调和40个miRNAs表达量上调，靶基因分析发现差异表达的miR-138、miR-196a与HSP家族HSPA4L和HSPH1有关；热应激条件下有3类miRNAs进行调控，在大部分应激表达miRNAs，如miR125b、miR-222、miR-22和let-7c；只在高温诱导下表达miRNAs，如miR-452、miR-382和miR-378；和在应激条件下表达下调的miRNAs。高温抑制miRNA-24的表达，降低奶牛乳腺上皮细胞凋亡发生率，促进细胞的生长发育[21]。热应激刺激CYP2e基因生产大量活性氧自由基[22]，造成细胞内限速酶肌肉磷酸果糖激酶(PFKm)表达量上升，糖酵解加快，乳酸浓度升高；长期应激会使乳酸在细胞内堆积，导致微环境的酸中毒，使细胞凋亡。而miR-320a靶向调控PFKm，抑制糖酵解[23]。
热应激能影响细胞内HSP表达，进行急性稳态反应，如HSP和相关基因表达改变[15]。有研究发现HSP70和HSP90与Ago2(RISC重要组成部分，对miRNAs修饰作用)有关，可能HSP还参与miRNA的基因沉默[24]。但Fukuoka等[25]发现miRNAs的表达水平不变情况下，热应激能使基因沉默活性加强；HSP90对miRNAs基因沉默没有作用，HSP1也不参与miRNAs介导的基因沉默；认为内源miRNAs基因沉默在抑制热变性蛋白可能只起辅助的作用。
2.2 对热应激畜禽免疫和抗应激的调控热应激反应是机体通过启动自身防御体系，以避免机体损伤的一种非特异性防御反应，但强度过大、时间过长，机体出现病理、器官衰竭甚至死亡[26]。研究发现热应激促使泛素-蛋白酶体通路表达上调，清除严重受损蛋白质[27]；机体下丘脑-垂体-肾上腺素轴活性加强，加强机体抗应激能力。Zheng等[28]研究热应激奶牛血液中miRNAs表达谱发现，有7个miRNAs涉及应激和免疫有关；其中表达上调miR-19a和miR-19b通过对靶基因HSP家族调控，参与热应激调节。在急性应激下大鼠循环血中HSP72浓度上调和miR-142-5P、miR-203下调[29]。miR-142-5P通过调控白细胞介素(IL)-6受体进行免疫反应；miR-203能抑制细胞因子信号传导抑制蛋白-3(SOCS3)，进而调控促炎症的细胞因子[30]。蔡明成等[31]研究热应激对红安格斯母牛外周血miRNAs的影响发现有118个miRNAs表达上调，197个miRNAs表达下调；将表达量显著上调和下调的10个miRNAs进行靶基因预测发现，miRNAs表达上调的靶基因主要参与细胞增殖、凋亡的调节，miRNAs表达下调的靶基因主要参与机体免疫功能的调节。其中，miR-98靶向调控IL-6基因的表达[32]，miR-31靶向调控核转录因子kappa B(NF-κB)诱导激酶(NIK)的表达，调节炎症反应[33]。以上研究表明，在热应激条件下畜禽可通过miRNAs调控靶基因表达，参与机体免疫和抗应激反应。
2.3 对热应激畜禽器官损伤的调控 2.3.1 肠道热应激畜禽肠道缺血缺氧，造成肠道黏膜损伤[22]。miRNAs在此过程发挥重要作用。McKenna等[34]对小鼠空肠组织黏膜层采用高通量测序，检测到1 094个成熟miRNAs，其中有65个是小肠黏膜特异性表达的miRNAs；当Dicer1酶(miRNAs合成酶)基因缺失，小鼠肠上皮组织紊乱，肠屏障功能受损，发生炎症反应。Yu等[7]研究热应激引起大鼠小肠损伤发现，有18个miRNAs(含miR-34a、miR-34b、miR-140、miR-375、miR-500)的表达量上调和11个miRNAs(含miR-31)的表达量下调。miR-500能靶向已糖激酶2(hexokinase 2，HK2)mRNA的3′UTR区域，通过降低HK2的活性，抑制小肠葡萄糖的吸收[35]。miR-375作用于IL-13，调控T细胞2中促上皮细胞因子胸腺基质淋巴细胞生成素(TSLP)的表达，使抵抗素样分子家族β(RELMβ)表达降低，使肠道黏膜免疫力缺失[36]。miR-34a、miR-34b可靶向作用于凋亡基因(p53)，调控DNA损伤修复、细胞周期阻滞、细胞凋亡[37]。miR-140调节机体的炎症反应[38]。miR-31在炎症反应时表达量下调，与细胞生长、死亡和细胞通信的相关基因有关[39]。
热应激能导致肠道脂多糖(LPS)显著上升和肠黏膜屏障受损，LPS进入肝脏却无法全部被消除，进而进入循环系统，进行全身炎症反应[40, 41]。LPS会通过NF-κB信号通路激活肿瘤坏死因子-α(TNF-α)和IL-6，通过SOCS3导致肝脏胰岛素耐受和产生高胰岛素血症，胰岛素信号通路与炎症因子的信号传导存在交叉作用[42, 43]。当LPS刺激时，IL-6分泌和miR-181b表达呈负相关[44]。肠道黏膜的miR-146a表达量上调，通过抑制Toll样受体(TLR)信号通路中IL-1受体相关激酶1(IRAK1)，保护肠道免受损伤[45]。miR-140作为细胞因子信号抑制蛋白3(SOCS3)的作用靶标，调控LPS引起炎症反应[46]。总之，在热应激条件下肠道产生大量的LPS，通过TLR和NF-κB信号通路刺激促炎症因子的释放，引起炎症反应；而miRNAs通过调控TLR和NF-κB信号通路上相关基因，保护肠道健康。
2.3.2 肝脏热应激容易导致肝脏氧化损伤。而肝脏中谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)能清除氧自由基，减小热应激对肝脏氧化损伤[47]。miR-214靶向作用谷胱甘肽S-转移酶(MGST1)，调节抗氧化能力[47]。另外，肝细胞中线粒体是呼吸链氧自由基的主要产生部位，miR-93和miR-214靶向调控肝脏细胞色素c复合物(UQCRC1)，起保护肝功能的作用[48, 49]。
2.4 对热应激畜禽生产性能的调控在热应激条件下，畜禽增加排汗、加快心跳和呼吸频率来维持机体的稳态，但影响畜禽的生产性能[50]。如热应激奶牛采食量下降，营养物质摄入量不足，引起奶牛能量负平衡，导致产奶量降低[51]。Baumgard等[51]报道热应激奶牛出现能量负平衡，将葡萄糖优先在组织中进行代谢利用而非泌乳。miR-143通过抑制胰岛素及下游因子蛋白激酶B(AKT)的活性，调控葡萄糖的稳态[53]。Fatima等[54]采用基因芯片技术检测能量负平衡状态奶牛肝脏miRNAs表达时发现，有miR-17-5p、miR-31、miR-140、miR-1281和miR-2885这5个miRNAs表达上调，其中miR-31的靶基因肝细胞核因子3-γ(HNF3-γ)和转录因子(TF)涉及胰岛素样生长因子-1(IGF-1)表达调控，与葡萄糖代谢的稳态有关。营养缺乏时，miR-80表达量下调，直接靶向CRBE-1和调控胰岛素信号通路调节机体能量代谢[55]。由此可见，热应激畜禽可通过miRNAs作用调控机体能量代谢，进而影响采食量。
热应激影响畜禽产品的质量。热应激降低牛奶中乳蛋白和酪蛋白浓度，产生“热应激乳蛋白降低征”[56, 57, 58]。张凡建等[59]发现不同热应激程度对牛奶品质的影响也不同；中度热应激奶牛乳蛋白率极显著低于轻度热应激，而重度热应激奶牛乳脂率显著低于轻度热应激。miR-199a-3p能通过调控AKT/雷帕霉素靶蛋白(mTOR)信号通路来调控蛋白的合成[60]。miR-15a靶向作用于生长激素受体，能抑制乳腺上皮细胞增殖和酪蛋白的分泌[61]。miR-200a靶向作用于乳脂合成关键基因信号转导和转录活化蛋白4(STAT4)，调控乳脂合成[62]。miR-142-3P靶向作用于催乳素受体，可调控乳腺上皮细胞酪蛋白和甘油三酯的分泌[63]。热应激降低畜禽骨骼肌中脂肪含量，提高腹部脂肪含量，引起肌肉组织中不饱和脂肪酸氧化，产生异味，降低肉品质[64]。miR-130能靶向调控过氧化物酶体增殖物激活受体γ(PPARγ)，调节脂肪细胞分化和脂肪沉积[65]。miR-27b通过靶向作用于脂蛋白脂肪酶(LPL)基因和调控丝裂原活化蛋白激酶(MAPK)、Wnt等信号通路抑制肉牛肌内脂肪的沉积[66]。
2.5 对热应激家畜繁殖性能的调控热应激影响畜禽精子活力，降低受胎率，导致胚胎早亡和增加流产率[67]。Ji等[68]研究高温和氧化应激能降低精子的miR-15表达量，并通过靶向结合HSPA1B的3′UTR区域，减小应激对精子产生的损伤。研究发现miRNAs对机体繁殖发育起到重要作用，从单细胞分裂增殖形成4-细胞期时，miRNAs经历先减少后增加的过程；其中miR-290家簇上调15倍，通过抑制靶基因Dickkopf相关蛋白1(Dkk-1)激活Wnt信号通路，为机体的胚胎形成、发育和干细胞分化发挥重要作用[69, 70]。Nehammer等[71]研究发现热应激影响产蛋率；与野生型相比，miR-80突变型秀丽隐杆线虫的产蛋率28 ℃时显著降低，而miR-71、miR-80和miR-239突变型秀丽隐杆线虫在30 ℃时几乎不产蛋；并认为在高温下，miRNAs基因缺失型秀丽隐杆线虫减少产蛋原因可能是特性miRNAs损伤可以使性腺变得敏感或者缺失特异性miRNAs的胚胎在高温下无法生存。上述研究证实，畜禽可通过miRNAs作用缓解热应激对繁殖性能的损害。
3 小 结miRNAs作为一种转录后调控机制，在热应激条件miRNAs在细胞生长、凋亡，机体免疫和抗应激反应、生长性能和繁殖性能等多方面发挥重要的调控作用。因此，探讨miRNAs在热应激条件下对机体调控作用，差异表达miRNAs、miRNAs家族的协调作用及其靶基因的调控网络或信号通路，有助于利用热应激分子特征研究，缓解热应激对机体造成损伤。
| [1] | 黄茹华,张巧娥,苏嘉羽,等.宁夏地区不同季节牛乳成分的比较[J]. 黑龙江畜牧兽医:科技版,2013(12):77-79. ( 1)
|
| [2] | 宋代军,何钦,姚焰础.热应激对不同泌乳阶段奶牛生产性能和血清激素浓度的影响[J]. 动物营养学报,2013,25(10):2294-2302. (1)
|
| [3] | FRIEDMAN J R,KAESTNER K H.The foxa family of transcription factors in development and metabolism[J]. Cellular and Molecular Life Sciences CMLS,2006,63(19/20):2317-2328. (1)
|
| [4] | FRIEDMAN R C,FARH K K H,BURGE C B,et al.Most mammalian mRNAs are conserved targets of microRNAs[J]. Genome Research,2009,19(1):92-105. (1)
|
| [5] | SUN W,LI Y S J,HUANG H D,et al.MicroRNA:a master regulator of cellular processes for bioengineering systems[J]. Annual Review of Biomedical Engineering,2010,12:1-27. (1)
|
| [6] | YU J,YIN P,LIU F,et al.Effect of heat stress on the porcine small intestine:a morphological and gene expression study[J]. Comparative Biochemistry and Physiology-Part A:Molecular and Integrative Physiology,2010,156(1):199-128. (1)
|
| [7] | YU J,LIU FH,YIN P,et al.IntegratingmiRNA and mRNA expression profiles in response to heat stress-induced injury in rat small intestine[J]. Functional &Integrative Genomics,2011,11(2):203-213. (2)
|
| [8] | FILIPOWICZ W,BHATTACHARYYA S N,SONENBERGN.Mechanisms of post-transcriptional regulation by microRNAs:are the answers in sight[J]. Nature Reviews Genetics,2008,9(2):102-114. (2)
|
| [9] | AMBROSV.MicroRNA pathways in flies and worms:growth,death,fat,stress,and timing[J]. Cell,2003,113(6):673-676. (1)
|
| [10] | LEE R C,FEINBAUM R L,AMBROSV.The Celegansheterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J]. Cell,1993,75(5):843-854. (1)
|
| [11] | HAN J J,LEE Y,YEOM K H,et al.The Drosha-DGCR8 complex in primary microRNA processing[J]. Genes & Development,2004,18(24):3016-3027. (1)
|
| [12] | KIM V N.MicroRNA precursors in motion:exportin-5 mediates their nuclear export[J]. Trends in Cell Biology,2004,14(4):156-159. (1)
|
| [13] | ZENG Y.Principles of micro-RNA production and maturation[J]. Oncogene,2006,25(46):6156-6162. (1)
|
| [14] | BAEK D,VILLÉN J,SHIN C,et al.The impact of microRNAs on protein output[J]. Nature,2008,455(7209):64-71. (1)
|
| [15] | RHOADS R P,BAUMGARD L H,SUAGEE J K,et al.Nutritional interventions to alleviate the negative consequences of heat stress[J]. Advances in Nutrition,2013,4(3):267-276. (2)
|
| [16] | LI X R,CAI M J.Recovery of the yeast cell cycle from heat shock-induced G1 Arrest involves a positive regulation of G1cyclin expression by the S phase cyclin Clb5[J]. Journal of Biological Chemistry,1999,274(34):24220-24231. (1)
|
| [17] | COLLIER R J,STIENING C M,POLLARD B C,et al.Use of gene expression microarrays for evaluating environmental stress tolerance at the cellular level in cattle[J]. Journal of Animal Science,2006,84:1-13. (1)
|
| [18] | 汤建中,张涛,丁淑琴,等.pSicoR/miR-17-5p靶向调控UNC-51样激酶1(ULK1)及其对细胞自噬的影响[J]. 临床检验杂志,2014,3(3):698-704. (1)
|
| [19] | BOULIAS K,HORVITZ H R.The C.elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO[J]. Cell Metabolism,2012,15(4):439-450. (1)
|
| [20] | WILMINK G J,ROTH C L,IBEY B L,et al.Identification of microRNAs associated with hyperthermia-induced cellular stress response[J]. Cell Stress and Chaperones,2010,15(6):1027-1038. (1)
|
| [21] | 李惠侠,王振云,张震,等.高温条件下miRNA-24对奶牛乳腺上皮细胞增殖与凋亡的影响[J]. 中国农业科学,2010,43(22):4732-4738. (1)
|
| [22] | MURAKAMI A E,SAKAMOTO M I,NATALI M R M,et al.Supplementation of glutamine and vitamin E on the morphometry of the intestinal mucosa in broiler chickens[J]. Poultry Science,2007,86(3):488-495. (2)
|
| [23] | TANG H B,LEE M,SHARPE O,et al.Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems[J]. The FASEB Journal,2012,26(11):4710-4721. (1)
|
| [24] | IWASAKI S,KOBAYSHI M,YODA M,et al.Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes[J]. Molecular Cell,2010,39(2):292-299. (1)
|
| [25] | FUKUOKA M,YOSHIDA M,EDA A,et al.Gene silencing mediated by endogenous microRNAs under heat stress conditions in mammalian cells[J]. PLoS One,2014,9(7):e103130. (1)
|
| [26] | 刘丽莉,谢红兵,杨永生,等.基因芯片筛选畜禽热应激差异表达基因的研究进展[J]. 动物营养学报,2012,24(12):2287-2294. (1)
|
| [27] | KOLLI V,UPADHYAY R C,SINGH D.Peripheral blood leukocytes transcriptomic signature highlights the altered metabolic pathways by heat stress in zebu cattle[J]. Research in Veterinary Science,2014,96(1):102-110. (1)
|
| [28] | ZHENG Y,CHEN K L,ZHENG X M,et al.Identification and bioinformatics analysis of microRNAs associated with stress and immune response in serum of heat-stressed and normal Holstein cows[J]. Cell Stress and Chaperones,2014,19(6):973-981. (1)
|
| [29] | BENINSON L A,BROWN P N,LOUGHRIDGE A B,et al.Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)[J]. PLoS One,2014,9(9):e108748. (1)
|
| [30] | RU P,STEELE R,HSUEH E C,et al.Anti-miR-203 upregulatesSOCS3 expression in breast cancer cells and enhances cisplatinchemosensitivity[J]. Genes &Cancer,2011,2(7):720-727. (1)
|
| [31] | 蔡明成.热应激对肉牛生理生化指标及外周血microRNA表达水平的影响[D]. 硕士学位论文.重庆:西南大学,2014. (1)
|
| [32] | WONG P K K,CAMPBELL I K,EGAN P J,et al.The role of the interleukin-6 family of cytokines in inflammatory arthritis and bone turnover[J]. Arthritis & Rheumatism,2003,48(5):1177-1189. (1)
|
| [33] | THU Y M,RICHMOND A.NF-κB inducing kinase:a key regulator in the immune system and in cancer[J]. Cytokine & Growth Factor Reviews,2010,21(4):213-226. (1)
|
| [34] | MCKENNA L B,SCHUG J,VOUREKA S A,et al.MicroRNAs control intestinal epithelial differentiation,architecture,and barrier function[J]. Gastroenterology,2010,139(5):1654-1664. (1)
|
| [35] | 金晓露,杨建香,李真,等.乳腺发育及泌乳相关miRNA研究进展[J]. 遗传,2013,35(6):695-702. (1)
|
| [36] | BITON M,LEVIN A,SLYPER M,et al.Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk[J]. Nature Immunology,2011,12(3):239-246. (1)
|
| [37] | ANTONINI D,RUSSO M T,DE ROSAL,et al.Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells[J]. Journal of Investigative Dermatology,2010,130(5):1249-1257. (1)
|
| [38] | QIN H W,NIYONGERE S A,LEE S J,et al.Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes[J]. The Journal of Immunology,2008,181(5):3167-3176. (1)
|
| [39] | NAEEM A,ZHONG K,MOISÁ S J,et al.Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis[J]. Journal of Dairy Science,2012,95(11):6397-6408. (1)
|
| [40] | PLAIZIER J C,KHAFIPOURE,LIS,et al.Subacuteruminal acidosis (SARA),endotoxins and health consequences[J]. Animal Feed Science and Technology,2012,172(1/2):9-21. (1)
|
| [41] | KHAFIPOUR E,KRAUSE D O,PLAIZIER J C.A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation[J]. Journal of Dairy Science,2009,92(3):1060-1070. (1)
|
| [42] | BABON J J,VARGHESE L N,NICOLA N A.Inhibition of IL-6 family cytokines by SOCS3[J]. Seminars in Immunology,2014,26(1):13-19. (1)
|
| [43] | 尤巧英,李成江.部分炎症因子与胰岛素抵抗[J]. 国外医学内分泌学分册,2004,24(3):183-185. (1)
|
| [44] | ZHANG W J,SHEN X J,XIE L Y,et al.MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage RAW264.7 cells[J]. Journal of Inflammation,2015,12:18. (1)
|
| [45] | CHASSIN C,KOCUR M,POTT J,et al.MiR-146a mediates protective innate immune tolerance in the neonate intestine[J]. Cell Host &Microbe,2010,8(4):358-368. (1)
|
| [46] | QIN H W,NIYONGERE S A,LEE S J,et al.Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes[J]. The Journal of Immunology,2008,181(5):3167-3176. (1)
|
| [47] | 王菲,黄毅,李延森,等.Keap1/Nrf2/ARE通路相关基因在热诱导的氧化应激小鼠肝脏中的表达[J]. 中国生物化学与分子生物学报,2014,30(3):284-290. (2)
|
| [48] | VANBALKOM B W M,DE JONG O G,SMITSM,et al.Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells[J]. Blood,2013,121(19):3997-4006. (1)
|
| [49] | MAES O C,AN J,SAROJINI H,et al.Murine microRNAs implicated in liver functions and aging process[J]. Mechanisms of Ageing and Development,2008,129(9):534-541. (1)
|
| [50] | KADZERE C T,MURPHY M R,SILANIKOVE N,et al.Heat stress in lactating dairycows:a review[J]. Livestock Production Science,2002,77(1):59-91. (1)
|
| [51] | WHEELOCK J B,RHOADS R P,VANBAALE M J,et al.Effects of heat stress on energetic metabolism in lactating Holstein cows[J]. Journal of Dairy Science,2010,93(2):644-655. (1)
|
| [52] | BAUMGARD L H,ABUAJAMIEH M K,STOAKES S K,et al.Feeding and managing cows to minimize heat stress[C]//Proceedings of the 23rd Tri-State Dairy Nutrition Conference,Fort Wayne,Indiana,USA,14-16 April 2014.Columbo:Ohio State University,2014:61-74. (0)
|
| [53] | JORDANS D,KRVGER M,WILLMES D M,et al.Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism[J]. Nature Cell Biology,2011,13(4):434-446. (1)
|
| [54] | FATIMA A,WATERS S,O’BOYLE P,et al.Alterations in hepatic miRNA expression during negative energy balance in postpartum dairy cattle[J]. BMC Genomics,2014,15:28. (1)
|
| [55] | JIANG Y,LANGLEY B,LUBIN F D,et al.Epigenetics in the nervous system[J]. The Journal of Neuroscience,2008,28(46):11753-11759. (1)
|
| [56] | BERNABUCCI U,BASIRICÒ L,MORERA P,et al.Effect of summer season on milk protein fractions in Holstein cows[J]. Journal of Dairy Science,2015,98(3):1815-1827. (1)
|
| [57] | COWLEY F C,BARBER D G,HOULIHAN A V,et al.Immediate and residual effects of heat stress and restricted intake on milk protein and casein composition and energy metabolism[J]. Journal of Dairy Science,2015,98(4):2356-2368. (1)
|
| [58] | 程建波,王伟宇,郑楠,等.自然生产条件下热应激周期变化揭示泌乳中期奶牛出现"热应激乳蛋白降低征"[J]. 中国畜牧兽医,2014,41(10):73-84. (1)
|
| [59] | 张凡建,徐聪,翁晓刚,等.不同程度热应激对泌乳中期奶牛产奶量和乳成分的影响[J]. 中国兽医学报,2014,34(10):1686-1688. (1)
|
| [60] | SHEN L,SUN C M,LI Y Y,et al.MicroRNA-199a-3p suppresses glioma cell proliferation by regulating the AKT/mTOR signaling pathway[J]. Tumor Biology,2015,36(9):6929-6938. (1)
|
| [61] | LI H M,WANG C M,LI Q Z,et al.MiR-15a decreases bovine mammary epithelial cell viability and lactation and regulates growth hormone receptor expression [J]. Molecules,2012,17(10):12037-12048. (1)
|
| [62] | 张犁苹,罗军,林先滋,等.miR-200家族在西农萨能奶山羊乳腺组织中的表达分析[J]. 畜牧兽医学报,2013,44(6):944-951. (1)
|
| [63] | 李慧铭.miR-142-3p对小鼠乳腺发育和泌乳重要功能基因Prlr的表达调控[D]. 博士学位论文.哈尔滨:东北农业大学,2013. (1)
|
| [64] | 冯跃进,顾宪红.热应激对猪肉品质的影响及其机制的研究进展[J]. 中国畜牧兽医,2013,40(2):96-99. (1)
|
| [65] | 李虹仪,习欠云,张永亮.miR-130a在猪皮下脂肪细胞分化中的调节作用[J]. 中国生物化学与分子生物学报,2014,30(12):1216-1222. (1)
|
| [66] | 汪海洋,郑月,李惠侠,等.西门塔尔牛肌内和皮下脂肪miRNA表达谱及miR-27b靶基因分析[J]. 中国农业科学,2013,46(18):3894-3900. (1)
|
| [67] | DE RENSIS F,GARCIA-ISPIERTO I,LÓPEZ-GATIUS F.Seasonalheat stress:clinical implications and hormone treatments for the fertility of dairy cows[J]. Theriogenology,2015,84(5):659-666. (1)
|
| [68] | JI Z L,LU R J,MOU L S,et al.Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele[J]. Reproduction,2014,147(5):693-701. (1)
|
| [69] | TANG F C,KANEDA M,CARROLL D O,et al.Maternal microRNAs are essential for mouse zygotic development[J]. Genes &Development,2007,21(6):644-648. (1)
|
| [70] | ZOVOILIS A,SMORAG L,PANTAZI A,et al.Members of the miR-290 cluster modulate in vitro differentiation of mouse embryonic stem cells[J]. Differentiation,2009,78(2/3):69-78. (1)
|
| [71] | NEHAMMER C,PODOLSKA A,MACKOWIAK S D,et al.Specific microRNAs regulate heat stress responses in Caenorhabditiselegans[J]. Scientific Reports,2015,5:8866. (1)
|