哺乳期及断奶后饲喂不同日粮仔猪小肠发育全基因组表达谱研究
|
摘要
为了探讨哺乳期和断奶后饲喂不同日粮的仔猪小肠发育的分子机制,本研究利用猪全基因组表达谱芯片进行两个试验,分析不同生长发育阶段仔猪小肠全基因组转录谱的变化,并对差异表达基因进行不同层次的数据挖掘。结果如下:
试验一哺乳仔猪小肠发育全基因组转录谱研究
仔猪小肠发育对动物的生长具有重要意义。本试验利用猪表达谱芯片,检测大约克哺乳仔猪(出生0d,3d,8d,14d和21d)肠道转录谱变化,结果如下:
1、全基因组转录谱芯片(PGA)分析结果:序列试验基因表达模式分析(STC)得到80个表达模式,其中模式66和13达极显著水平(p＜0.01),提示哺乳阶段仔猪小肠发育与这些模式所属基因差异表达有关。
2、对6个差异表达基因进行qRT-PCR验证结果:两种实验方法检测结果均为正相关,相关系数为0.934±0.025,表明本研究结果准确可靠,检测数据能够真实反映基因的表达变化规律。
3、上调模式66所属基因Gene Ontology(GO)分析结果:该簇基因涉及的显著生物学过程(BP)主要有细胞周期及促进真菌类细胞壁的形成等(p＜0.01)。下调模式13所属基因GO分析发现,该簇基因涉及的显著BP主要有维生素及离子转运等(p＜0.01)。提示这些生物学过程对新生仔猪肠道发育具有重要意义。
4、通径分析结果:差异表达基因主要涉及细胞色素参与的外源物质代谢及亚麻油酸代谢等通路发生了扰动,从一定程度上揭示了肠道发育过程的分子基础。
5、基因共表达网络构建和分析:调控网络的构建从一定程度上反映了肠道发育过程的复杂性,同时还鉴定出20个在网络中具有重要调控能力的基因,建议作为对肠道发育具有重要影响和研究价值的种子基因进行深入研究。
试验二不同蛋白源对断奶仔猪小肠全基因组转录谱的影响
断奶日粮对仔猪小肠发育的影响是显著的。为了探讨不同蛋白源日粮对仔猪小肠发育影响的差异,本试验利用猪表达谱芯片,检测不同蛋白源日粮下断奶仔猪(断奶0d,3d,8d和14d)小肠转录谱,结果如下:
1、PGA结果:乳源蛋白替代30%总蛋白组(处理1)获得370个差异表达基因。STC分析得到26个显著模式中,模式5和11显著性水平最高(p＜0.01),全植物蛋白日粮处理(处理2)获得263个差异表达基因。STC分析得到26个主流模式,其中模式3和22显著水平最高(p＜0.01)。提示不同蛋白源日粮对小肠的影响和这些模式所属基因差异表达相关。
2、分别对6个差异表达基因进行qRT-PCR验证结果:芯片结果和qRT-PCR结果均为正相关,相关系数分别为0.902±0.023和0.855±0.036。表明本研究结果准确可靠,检测数据能够真实反映基因的表达变化规律。
3、GO分析结果:乳源蛋白组模式5所属基因涉及的显著BP包括提高细胞内钙离子浓度等,模式11所属基因涉及的显著BP有对外加营养刺激的反应等(p＜0.01)。在植物蛋白组中,模式3所属基因涉及的显著BP主要有正向调节平滑肌收缩等,模式22所属基因涉及外皮细胞的生长等分子事件(p＜0.01)。提示不同断奶日粮下,差异基因主要体现了这些生物学过程。
4、通径分析结果:不同蛋白源日粮组转录谱差异表达基因参与的信号通路相似,主要显著通路有PPAR信号通路、氨基糖代谢、T细胞受体信号通路以及脂肪代谢等通路(p＜0.01)。提示这些通路对断奶后小肠发育具有重要意义。
5、基因共表达网络构建和分析:基因共表达网络一定程度上揭示了不同蛋白源日粮对肠道发育影响的明显差异。同时分别鉴定出12个和9个在两个处理调控网络中具有重要影响力基因以及9个在两个处理中的网络调控地位发生改变的共表达基因。建议可作为影响不同蛋白源日粮下肠道发育关键基因进行研究。
本研究筛选出了对仔猪肠道发育可能具有重要影响和研究价值的基因,初步揭示了生长发育过程中肠细胞基因表达的规律、互作关系以及不同蛋白源日粮下肠道发育差异的分子基础。
To investigate the molecular mechanism of intestinal development of postnatal piglets during suckling and after weaming fed with different weanling diets in this study, two experiments were conducted by using porcine genome array to analyze the transcription profile of piglets during different growth and development stages. The differentially expressed genes were screened and these data were mined. The results were as followings:
Experiment 1. Transcription profile of whole-genome for the developmental intestine of suckling piglets
The intestinal development of postnatal piglets has an important impact on health and growth performance. The transcription profiles of nursing Yorkshire at the age of 0, 3, 8, 14 and 21 days were detected by using porcine genome array (PGA) in this study. The results were as followings:
1. The results of PGA during suckling: More than 8000 differentially expressed transcripts in intestine of piglets during suckling were obtained. Series Test Cluster were analyzed for these differential expression genes and 80 profiles were established, among which profiles 66 and 13 were the most significant (P<0.01). This result indicated that the differentially expressed genes in co-expression of these trends are related to the intestinal development during suckling.
2. Six differentially expressed genes were selected and quantified by qRT-PCR. Results illustrated the expression patterns of the six genes were similar to those from PGA. The two experimental methods were both positively correlated with correlation coefficient being 0.934±0.025. This result demonstrateed that the microarray technique used in this study is accurate and reproducible.
3. Gene Ontology(GO)analysis of the profile 66 indicated that the co-expression genes in this profile were mainly involved in cell cycle and fungal-type cell wall organization. GO of the profile 13 showed that the co-expression genes in this profile were mainly involved in vitamin and ionic transports. Furthermore, there was a significant inflection point on d3 of age, which suggested that d3 of age was a crucial period for piglets.
4. Significant pathway analysis of differentially expressed genes in profiles 66 and 13 indicated that the pathways which the differentially expressed genes participated during suckling were mainly PPAR signaling pathway, linoleic acid metabolism and so on. This result suggested that these pathways were important to the intestinal development.
5. Construction and analysis of gene regulatory networks (GRNs) initially revealed that there were 20 genes which possessed important regulatory ability (p<0.01), These genes could regulate other genes in GRN.
Experiment 2. Effect of different weaning diets on transcription profile of genome-wide in intestine for weanling piglets
The weanling diets have an obvious impact on the intestinal development. To investigate the impact of different weaning diets on the intestinal development, in the present study, PGA was employed to detect the difference on transcription spectrum of intestine for weanling piglets fed with different diets with or without milk protein.
1. Results of PGA: Analysis of expression profiles in genome-wide transcription in weanling piglets fed with the diets with milk protein (treatment 1) was conducted and 370 differentially expressed transcripts were screened. Among these model profiles, there were 26 significant profiles and profiles 5 and 11 were the most significant (P<0.01). Meanwhile, analysis of expression profiles in genome-wide transcription in weanling piglets fed with the vegetable protein without milk protein (treatment 2) showed that 263 differentially expressed transcripts were screened. Series Test Cluster were analyzed for these differential expression genes and 26 significant profiles were obtained, among these model profiles, profiles 3 and 22 were the most significant (P<0.01). This result indicated that the differentially expressed genes in co-expression of these trends are related to the intestinal development of weanling piglets.
2. Six differentially expressed genes were selected and quantified by qRT-PCR. Results illustrated that the expression patterns of the six genes were similar to those from PGA. The two experimental methods were both positively correlated with correlation coefficient being 0.902±0.023 and 0.855±0.036. These resultes indicated that the microarray technique used in this study is accurate and reproducible.
3. The co-expression of genes in these significant profiles were assayed using GO: For the treatment 1, it was found from the results of GO that the genes in profile 5 were mainly involved in some biology process such as tachykinin signaling pathway, elevation of Cytosolic calcium ion concentration and so on, while the genes in profile 11 were mainly involved in positive regulation of viral transcription, inflammatory response, histidine metabolic process, cellular metabolic process (p<0.01) and so on. For the treatment 2, the results of GO revealed that the genes in profile 3 were mainly involved in positive regulation of smooth muscle contraction, while the genes in profile 22 were mainly involved in cell growth.
4. Pathway analysis: The signal pathways that the differentially expressed genes participated in both treatments were similar, including PPAR signaling pathway, Aminosugars metabolism, T cell receptor signaling pathway and so on. These pathways changed obviously after weanling (p<0.01).
5. Construction and analysis of Dynamic-GeneNet of the differentially co-expression genes in significant profiles: Based on DGN model, gene regulatory networks (GRNs) for the genes in profile 5、11、3 and 22 in treatment land 2 were constructed. The GRNs revealed that there were 12 genes and 9 genes which possessed important regulatory ability in GRN. Meanwhile, 9 genes in these two GRNs were found to have changed the regulatory site. We can choose seed genes from sub-networks that have higher rank scores as potential key genes on the intestinal development of piglets.
These results highlight some possible candidate genes for developmental intestine of piglets and provide some data on which to base further study of the molecular mechanism of the developmental intestine of piglets.
试验一哺乳仔猪小肠发育全基因组转录谱研究
仔猪小肠发育对动物的生长具有重要意义。本试验利用猪表达谱芯片,检测大约克哺乳仔猪(出生0d,3d,8d,14d和21d)肠道转录谱变化,结果如下:
1、全基因组转录谱芯片(PGA)分析结果:序列试验基因表达模式分析(STC)得到80个表达模式,其中模式66和13达极显著水平(p＜0.01),提示哺乳阶段仔猪小肠发育与这些模式所属基因差异表达有关。
2、对6个差异表达基因进行qRT-PCR验证结果:两种实验方法检测结果均为正相关,相关系数为0.934±0.025,表明本研究结果准确可靠,检测数据能够真实反映基因的表达变化规律。
3、上调模式66所属基因Gene Ontology(GO)分析结果:该簇基因涉及的显著生物学过程(BP)主要有细胞周期及促进真菌类细胞壁的形成等(p＜0.01)。下调模式13所属基因GO分析发现,该簇基因涉及的显著BP主要有维生素及离子转运等(p＜0.01)。提示这些生物学过程对新生仔猪肠道发育具有重要意义。
4、通径分析结果:差异表达基因主要涉及细胞色素参与的外源物质代谢及亚麻油酸代谢等通路发生了扰动,从一定程度上揭示了肠道发育过程的分子基础。
5、基因共表达网络构建和分析:调控网络的构建从一定程度上反映了肠道发育过程的复杂性,同时还鉴定出20个在网络中具有重要调控能力的基因,建议作为对肠道发育具有重要影响和研究价值的种子基因进行深入研究。
试验二不同蛋白源对断奶仔猪小肠全基因组转录谱的影响
断奶日粮对仔猪小肠发育的影响是显著的。为了探讨不同蛋白源日粮对仔猪小肠发育影响的差异,本试验利用猪表达谱芯片,检测不同蛋白源日粮下断奶仔猪(断奶0d,3d,8d和14d)小肠转录谱,结果如下:
1、PGA结果:乳源蛋白替代30%总蛋白组(处理1)获得370个差异表达基因。STC分析得到26个显著模式中,模式5和11显著性水平最高(p＜0.01),全植物蛋白日粮处理(处理2)获得263个差异表达基因。STC分析得到26个主流模式,其中模式3和22显著水平最高(p＜0.01)。提示不同蛋白源日粮对小肠的影响和这些模式所属基因差异表达相关。
2、分别对6个差异表达基因进行qRT-PCR验证结果:芯片结果和qRT-PCR结果均为正相关,相关系数分别为0.902±0.023和0.855±0.036。表明本研究结果准确可靠,检测数据能够真实反映基因的表达变化规律。
3、GO分析结果:乳源蛋白组模式5所属基因涉及的显著BP包括提高细胞内钙离子浓度等,模式11所属基因涉及的显著BP有对外加营养刺激的反应等(p＜0.01)。在植物蛋白组中,模式3所属基因涉及的显著BP主要有正向调节平滑肌收缩等,模式22所属基因涉及外皮细胞的生长等分子事件(p＜0.01)。提示不同断奶日粮下,差异基因主要体现了这些生物学过程。
4、通径分析结果:不同蛋白源日粮组转录谱差异表达基因参与的信号通路相似,主要显著通路有PPAR信号通路、氨基糖代谢、T细胞受体信号通路以及脂肪代谢等通路(p＜0.01)。提示这些通路对断奶后小肠发育具有重要意义。
5、基因共表达网络构建和分析:基因共表达网络一定程度上揭示了不同蛋白源日粮对肠道发育影响的明显差异。同时分别鉴定出12个和9个在两个处理调控网络中具有重要影响力基因以及9个在两个处理中的网络调控地位发生改变的共表达基因。建议可作为影响不同蛋白源日粮下肠道发育关键基因进行研究。
本研究筛选出了对仔猪肠道发育可能具有重要影响和研究价值的基因,初步揭示了生长发育过程中肠细胞基因表达的规律、互作关系以及不同蛋白源日粮下肠道发育差异的分子基础。
To investigate the molecular mechanism of intestinal development of postnatal piglets during suckling and after weaming fed with different weanling diets in this study, two experiments were conducted by using porcine genome array to analyze the transcription profile of piglets during different growth and development stages. The differentially expressed genes were screened and these data were mined. The results were as followings:
Experiment 1. Transcription profile of whole-genome for the developmental intestine of suckling piglets
The intestinal development of postnatal piglets has an important impact on health and growth performance. The transcription profiles of nursing Yorkshire at the age of 0, 3, 8, 14 and 21 days were detected by using porcine genome array (PGA) in this study. The results were as followings:
1. The results of PGA during suckling: More than 8000 differentially expressed transcripts in intestine of piglets during suckling were obtained. Series Test Cluster were analyzed for these differential expression genes and 80 profiles were established, among which profiles 66 and 13 were the most significant (P<0.01). This result indicated that the differentially expressed genes in co-expression of these trends are related to the intestinal development during suckling.
2. Six differentially expressed genes were selected and quantified by qRT-PCR. Results illustrated the expression patterns of the six genes were similar to those from PGA. The two experimental methods were both positively correlated with correlation coefficient being 0.934±0.025. This result demonstrateed that the microarray technique used in this study is accurate and reproducible.
3. Gene Ontology(GO)analysis of the profile 66 indicated that the co-expression genes in this profile were mainly involved in cell cycle and fungal-type cell wall organization. GO of the profile 13 showed that the co-expression genes in this profile were mainly involved in vitamin and ionic transports. Furthermore, there was a significant inflection point on d3 of age, which suggested that d3 of age was a crucial period for piglets.
4. Significant pathway analysis of differentially expressed genes in profiles 66 and 13 indicated that the pathways which the differentially expressed genes participated during suckling were mainly PPAR signaling pathway, linoleic acid metabolism and so on. This result suggested that these pathways were important to the intestinal development.
5. Construction and analysis of gene regulatory networks (GRNs) initially revealed that there were 20 genes which possessed important regulatory ability (p<0.01), These genes could regulate other genes in GRN.
Experiment 2. Effect of different weaning diets on transcription profile of genome-wide in intestine for weanling piglets
The weanling diets have an obvious impact on the intestinal development. To investigate the impact of different weaning diets on the intestinal development, in the present study, PGA was employed to detect the difference on transcription spectrum of intestine for weanling piglets fed with different diets with or without milk protein.
1. Results of PGA: Analysis of expression profiles in genome-wide transcription in weanling piglets fed with the diets with milk protein (treatment 1) was conducted and 370 differentially expressed transcripts were screened. Among these model profiles, there were 26 significant profiles and profiles 5 and 11 were the most significant (P<0.01). Meanwhile, analysis of expression profiles in genome-wide transcription in weanling piglets fed with the vegetable protein without milk protein (treatment 2) showed that 263 differentially expressed transcripts were screened. Series Test Cluster were analyzed for these differential expression genes and 26 significant profiles were obtained, among these model profiles, profiles 3 and 22 were the most significant (P<0.01). This result indicated that the differentially expressed genes in co-expression of these trends are related to the intestinal development of weanling piglets.
2. Six differentially expressed genes were selected and quantified by qRT-PCR. Results illustrated that the expression patterns of the six genes were similar to those from PGA. The two experimental methods were both positively correlated with correlation coefficient being 0.902±0.023 and 0.855±0.036. These resultes indicated that the microarray technique used in this study is accurate and reproducible.
3. The co-expression of genes in these significant profiles were assayed using GO: For the treatment 1, it was found from the results of GO that the genes in profile 5 were mainly involved in some biology process such as tachykinin signaling pathway, elevation of Cytosolic calcium ion concentration and so on, while the genes in profile 11 were mainly involved in positive regulation of viral transcription, inflammatory response, histidine metabolic process, cellular metabolic process (p<0.01) and so on. For the treatment 2, the results of GO revealed that the genes in profile 3 were mainly involved in positive regulation of smooth muscle contraction, while the genes in profile 22 were mainly involved in cell growth.
4. Pathway analysis: The signal pathways that the differentially expressed genes participated in both treatments were similar, including PPAR signaling pathway, Aminosugars metabolism, T cell receptor signaling pathway and so on. These pathways changed obviously after weanling (p<0.01).
5. Construction and analysis of Dynamic-GeneNet of the differentially co-expression genes in significant profiles: Based on DGN model, gene regulatory networks (GRNs) for the genes in profile 5、11、3 and 22 in treatment land 2 were constructed. The GRNs revealed that there were 12 genes and 9 genes which possessed important regulatory ability in GRN. Meanwhile, 9 genes in these two GRNs were found to have changed the regulatory site. We can choose seed genes from sub-networks that have higher rank scores as potential key genes on the intestinal development of piglets.
These results highlight some possible candidate genes for developmental intestine of piglets and provide some data on which to base further study of the molecular mechanism of the developmental intestine of piglets.
引文
[1]Rothschild,Ruvinsky.Genetics of the Pig:CABI Press:Wallingford,UK;,1998.
[2]刘量衡.物质、信息、生命:中山大学出版社2001.
[3]Moughan PJ,Birtles M J,Cranwell PD,Smith WC,Pedraza M.The piglet as a model animal for studying aspects of digestion and absorption in milk-fed human infants.World Rev Nutr Diet 1992;67:40.
[4]Nabuurs MJ.Weaning piglets as a model for studying pathophysiology of diarrhea.Vet Q 1998;20Suppl 3:S42.
[5]Rothschild MF.Advances in pig genomics and functional gene discovery.Comp Funct Genomics 2003;4:266.
[6]Rothschild MF.Porcine genomics delivers new tools and results:this little piggy did more than just go to market.Genet Res 2004;83:1.
[7]Domeneghini C,Di Giancamillo A,Arrighi S,Bosi G.Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism.State of the art in the pig,and perspectives towards humans.Histol Histopathol 2006;21:273.
[8]Eubanks DL,Cooper R,Boring JG.Surgical technique for long-term cecal cannulation in the Yucatan minipig(Sus scrofa domestica).J Am Assoc Lab Anim Sci 2006;45:52.
[9]Reid G,Sanders ME,Gaskins HR,Gibson GR,Mercenier A,Rastall R,Roberfroid M,Rowland I,Cherbut C,Klaenhammer TR.New scientific paradigms for probiotics and prebiotics.J Clin Gastroenterol 2003;37:105.
[10]Society tAC.Cancer medicine.Hamilton.London,2003.
[11]王喜忠.细胞生物学.高等教育出版社2000.
[12]陆承平.兽医微生物学,中国农业出版社,2001.
[13]Cranwell PD.Development of the neonatal gut and enzyme systems,1995.
[14]王镜岩.生物化学:高等教育出版社,1999.
[15]北野宏明(日),刘笔锋(译).系统生物学基础:化学工业出版社,2007.
[16]Hiendleder S,Bauersachs S,Boulesteix A,Blum H,Arnold GJ,Frohlich T,Wolf E.Functional genomics:tools for improving farm animal health and welfare.Rev Sci Tech 2005;24:355.
[17]孙之荣(译),马尔科姆.坎贝尔.探索基因组学、蛋白组学和生物信息学,科学出版社出版,2005.
[18]Wintero AK,Fredholm M,Davies W.Evaluation and characterization of a porcine small intestine cDNA library:analysis of 839 clones.Mamm Genome 1996;7:509.
[19]Wernersson R,Schierup MH,Jorgensen FG,Gorodkin J,Panitz F,Staerfeldt HH,Christensen OF,Mailund T,Hornshoj H,Klein A,Wang J,Liu B,Hu S,Dong W,Li W,Wong GK,Yu J,Bendixen C,Fredholm M,Brunak S,Yang H,Bolund L.Pigs in sequence space:a 0.66X coverage pig genome survey based on shotgun sequencing.BMC Genomics 2005;6:70.
[20]Zhang H,Malo C,Boyle CR,Buddington RK.Diet influences development of the pig(Sus scrofa)intestine during the first 6 hours after birth.J Nutr 1998;128:1302.
[21]Zhang H,Malo C,Buddington RK.Suckling induces rapid intestinal growth and changes in brush border digestive functions of newborn pigs.J Nutr 1997;127:418.
[22]van Beers-Schreurs HM,Nabuurs MJ,Vellenga L,Kalsbeek-van der Valk HJ,Wensing T,Breukink HJ.Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood.J Nutr 1998;128:947.
[23]Tang M,Laarveld B,Van Kessel AG,Hamilton DL,Estrada A,Patience JF.Effect of segregated early weaning on postweaning small intestinal development in pigs.J Anim Sci 1999;77:3191.
[24]Inoue R,Tsukahara T,Nakanishi N,Ushida K.Development of the intestinal microbiota in the piglet.J Gen Appl Microbiol 2005;51:257.
[25]Thompson CL,Wang B,Holmes AJ.The immediate environment during postnatal development has long-term impact on gut community structure in pigs.ISME J 2008.
[26]Dvorak CM,Hirsch GN,Hyland KA,Hendrickson JA,Thompson BS,Rutherford MS,Murtaugh MP.Genomic dissection of mucosal immunobiology in the porcine small intestine.Physiol Genomics 2006;28:5.
[27] Trahair JF, Harding R. Ultrastructural anomalies in the fetal small intestine indicate that fetal swallowing is important for normal development: an experimental study. Virchows Arch A Pathol Anat Histopathol 1992;420:305.
[28] Kelly D, King TP, McFadyen M, Travis AJ. Effect of lactation on the decline of brush border lactase activity in neonatal pigs. Gut 1991;32:386.
[29] Blass EM, Teicher MH. Suckling. Science 1980;210:15.
[30] Hamosh M. Protective function of proteins and lipids in human milk. Biol Neonate 1998;74:163.
[31] James PS, Smith MW, Tivey DR, Wilson TJ. Dexamethasone selectively increases sodium-dependent alanine transport across neonatal piglet intestine. J Physiol 1987;393:569.
[32] Litin BS, Swan KR, Koldovsky O. Hormone maturative effect on perinatal rat colon glycosidases. J Pediatr Gastroenterol Nutr 1983;2:133.
[33] Plateroti M, Gauthier K, Domon-Dell C, Freund JN, Samarut J, Chassande O. Functional interference between thyroid hormone receptor alpha (TRalpha) and natural truncated TRDeltaalpha isoforms in the control of intestine development. Mol Cell Biol 2001;21:4761.
[34] Durant M, Gargosky SE, Dahlstrom KA, Hellman BH, Jr., Castillo RO. Regulation of postnatal intestinal maturation by growth hormone: studies in rats with isolated growth hormone deficiency. Pediatr Res 1996;40:88.
[35] W.N.Ewing, D.J.A.Cole, editors, the living gut, 1994.
[36] Domeneghini C, Di Giancamillo A, Savoini G, Paratte R, Bontempo V, Dell'Orto V. Structural patterns of swine ileal mucosa following L-glutamine and nucleotide administration during the weaning period. An histochemical and histometrical study. Histol Histopathol 2004;19:49.
[37] Madej M, Lundh T, Lindberg JE. Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets. Biol Neonate 1999;75:250.
[38] Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM. Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr 2008;138:24.
[39] Wu G. Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol 1997;272:G1382.
[40] Loret S, Brolet P, Pierzynowski S, Gouders I, Klimek M, Danielson V, Rosted A, Lesniewska V, Dandrifosse G. Pancreatic exocrine secretions as a source of luminal polyamines in pigs. Exp Physiol 2000;85:301.
[41] Tappenden KA, Albin DM, Bartholome AL, Mangian HF. Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story. J Nutr 2003;133:3717.
[42] Chowdhury SR, King DE, Willing BP, Band MR, Beever JE, Lane AB, Loor JJ, Marini JC, Rund LA, Schook LB, Van Kessel AG, Gaskins HR. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 2007;8:215.
[43] Maxwell SM. Sudden onset of blurred vision in a thirteen-year-old girl. Pediatr Infect Dis J 1995;14:1016.
[44] Kelly D, King TP, McFadyen M, Courts AG. Effect of preclosure colostrum intake on the development of the intestinal epithelium of artificially reared piglets. Biol Neonate 1993;64:235.
[45] 张宏福．仔猪营养生理与饲料配制技术研究,中国农业科技出版社,2000．
[46] Rawls JF, Samuel BS, Gordon JI. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci U S A 2004;101:4596.
[47] Su Y, Yao W, Perez-Gutierrez ON, Smidt H, Zhu WY. Changes in abundance of Lactobacillus spp. and Streptococcus suis in the stomach, jejunum and ileum of piglets after weaning. FEMS Microbiol Ecol 2008;66:546.
[48] Beagley KW, Husband AJ. Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 1998;18:237.
[49] 张宏福,李长忠．不同断奶日龄对仔猪消化酶发育规律的研究．中国农业科技出版社,2000．
[50] Bikker P, Dirkzwager A, Fledderus J, Trevisi P, le Huerou-Luron I, Lalles JP, Awati A. The effect of dietary protein and fermentable carbohydrates levels on growth performance and intestinal characteristics in newly weaned piglets. J Anim Sci 2006;84:3337.
[51] Garcia-Rodenas CL, Bergonzelli GE, Nutten S, Schumann A, Cherbut C, Turini M, Ornstein K, Rochat F, Corthesy-Theulaz I. Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J Pediatr Gastroenterol Nutr 2006;43:16.
[52] Helm RM, Golden C, McMahon M, Thampi P, Badger TM, Nagarajan S. Diet regulates the development of gut-associated lymphoid tissue in neonatal piglets.Neonatology 2007;91:248.
[53]Gilbert ER,Li H,Emmerson DA,Webb KE,Jr.,Wong EA.Dietary protein quality and feed restriction influence abundance of nutrient transporter mRNA in the small intestine of broiler chicks.J Nutr 2008;138:262.
[54]McCracken BA,Spurlock ME,Roos MA,Zuckermann FA,Gaskins HR.Weaning anorexia may contribute to local inflammation in the piglet small intestine.J Nutr 1999;129:613.
[55]Hampson DJ.Alterations in piglet small intestinal structure at weaning.Res Vet Sci 1986;40:32.
[56]Hall GA,Byrne TF.Effects of age and diet on small intestinal structure and function in gnotobiotic piglets.Res Vet Sci 1989;47:387.
[57]Mathers JC.Nutrient regulation of intestinal proliferation and apoptosis.Proc Nutr Soc 1998;57:219.
[58]Sanderson IR.Dietary regulation of genes expressed in the developing intestinal epithelium.Am J Clin Nutr 1998;68:999.
[59]Klurfeld DM.Nutritional regulation of gastrointestinal growth.Front Biosci 1999;4:D299.
[60]Wang J,Chen L,Li P,Li X,Zhou H,Wang F,Li D,Yin Y,Wu G.Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation.J Nutr 2008;138:1025.
[61]Reeds PJ,Burrin DG.Glutamine and the bowel.J Nutr 2001;131:25055.
[62]Biagi G,Piva A,Moschini M,Vezzali E,Roth FX.Effect of gluconic acid on piglet growth performance,intestinal microflora,and intestinal wall morphology.J Anim Sci 2006;84:370.
[63]李德发.猪的营养.中国农业科学技术出版社,2002.
[64]Makkink CA,Berntsen PJ,op den Kamp BM,Kemp B,Verstegen MW.Gastric protein breakdown and pancreatic enzyme activities in response to two different dietary protein sources in newly weaned pigs.J Anim Sci 1994;72:2843.
[65]Makkink CA,Negulescu GP,Qin G,Verstegen MW.Effect of dietary protein source on feed intake,growth,pancreatic enzyme activities and jejunal morphology in newly-weaned piglets.Br J Nutr 1994;72:353.
[66]E.Klipp,R.Herwig,A.Kowald,贺福初(译).系统生物学的理论、方法和应用.2007.
[67]Kitano H.Systems biology:a brief overview.Science 2002;295:1662.
[68]Kitano Ho Systems Biology:Toward System-level Understanding of Biological Systems.2001.
[69]Fields S,Song O.A novel genetic system to detect protein-protein interactions.Nature 1989;340:245.
[70]李瑶.基因芯片数据分析与处理:化学工业出版社,2006.
[71]Hood L,Heath JR,Phelps ME,Lin B.Systems biology and new technologies enable predictive and preventative medicine.Science 2004;306:640.
[72]Oltvai ZN,Barabasi AL.Systems biology.Life's complexity pyramid.Science 2002;298:763.
[73]Castrillo JI,Oliver SG.Yeast as a touchstone in post-genomic research:strategies for integrative analysis in functional genomics.J Biochem Mol Biol 2004;37:93.
[74]Millard AD,Tiwari B.Oligonucleotide microarrays for bacteriophage expression studies.Methods Mol Biol 2009;502:193.
[75]Li X,Zhu J,Huo H.Profile of differentially expressed genes in blood vessels and blood cells of hyperlipidemia rats using suppression subtractive hybridization.J Nanosci Nanotechnol 2005;5:1287.
[76]Tang Z.LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs.Genome Biology 2007;Volume 8,Issue 6,Article R115.
[77]Hoth S,Ikeda Y,Morgante M,Wang X,Zuo J,Hanafey MK,Gaasterland T,Tingey SV,Chua NH.Monitoring genome-wide changes in gene expression in response to endogenous cytokinin reveals targets in Arabidopsis thaliana.FEBS Lett 2003;554:373.
[78]Spinella DG,Bernardino AK,Redding AC,Koutz P,Wei Y,Pratt EK,Myers KK,Chappell G,Gerken S,McConnell SJ.Tandem arrayed ligation of expressed sequence tags(TALEST]:a new method for generating global gene expression profiles.Nucleic Acids Res 1999;27:e22.
[79]Tang Z.LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs.Genome Biology 2007;Volume 8,Issue 6,Article R115.
[80]杨志超.基于时间序列表达数据基因调控网络模型的研究进展.第二军医大学学报2008.
[81]Ernst J,Nau GJ,Bar-Joseph Z.Clustering short time series gene expression data.Bioinformatics 2005;21 Suppl 1:i159.
[82]Ramoni MF,Sebastiani P,Kohane IS.Cluster analysis of gene expression dynamics.Proc Natl Acad Sci U S A 2002;99:9121.
[83]Schliep A,Costa IG,Steinhoff C,Schonhuth A.Analyzing gene expression time-courses.IEEE/ACM Trans Comput Biol Bioinform 2005;2:179.
[84]Gotz S,Garcia-Gomez JM,Terol J,Williams TD,Nagaraj SH,Nueda MJ,Robles M,Talon M,Dopazo J,Conesa A.High-throughput functional annotation and data mining with the Blast2GO suite.Nucleic Acids Res 2008.
[85]Ashburner M,Ball CA,Blake JA,Botstein D,Butler H,Cherry JM,Davis AP,Dolinski K,Dwight SS,Eppig JT,Harris MA,Hill DP,Issel-Tarver L,Kasarskis A,Lewis S,Matese JC,Richardson JE,Ringwald M,Rubin GM,Sherlock G.Gene ontology:tool for the unification of biology.The Gene Ontology Consortium.Nat Genet 2000;25:25.
[86]Tomita M,Hashimoto K,Takahashi K,Shimizu TS,Matsuzaki Y,Miyoshi F,Saito K,Tanida S,Yugi K,Venter JC,Hutchison CA,3rd.E-CELL:software environment for whole-cell simulation.Bioinformatics 1999;15:72.
[87]Kanehisa M,Goto S.KEGG:kyoto encyclopedia of genes and genomes.Nucleic Acids Res 2000;28:27.
[88]Dahlquist KD,Salomonis N,Vranizan K,Lawlor SC,Conklin BR.GenMAPP,a new tool for viewing and analyzing microarray data on biological pathways.Nat Genet 2002;31:19.
[89]Suderman M,Hallett M.Tools for visually exploring biological networks.Bioinformatics 2007;23:2651.
[90]pevsner J,.生物信息学与功能基因组学:Chemical industry press,2006.
[91]Gonzalez G,Uribe JC,Tari L,Brophy C,Baral C.Mining gene-disease relationships from biomedical literature:weighting protein-protein interactions and connectivity measures.Pac Symp Biocomput 2007:28.
[92]YH Y,T S.Design issues for cDNA microarray experiments.Nat Rev Genet 2002;3:9.
[93]Chuaqui RF,Bonner RF,Best CJ,Gillespie JW,Flaig MJ,Hewitt SM,Phillips JL,Krizman DB,Tangrea MA,Ahram M,Linehan WM,Knezevic V,Emmert-Buck MR.Post-analysis follow-up and validation of microarray experiments.Nat Genet 2002;32 Suppl:509.
[94]Barrett T,Troup DB,Wilhite SE,Ledoux P,Rudnev D,Evangelista C,Kim IF,Soboleva A,Tomashevsky M,Edgar R.NCBI GEO:mining tens of millions of expression profiles—database and tools update.Nucleic Acids Res 2007;35:D760.
[95]霍永久.新生仔猪小肠生长发育及肠黏膜部分基 因的表达 南京农业大学学报2005:129-132
[96]Xu RJ,Mellor DJ,Tungthanathanich P,Birtles MJ,Reynolds GW,Simpson HV.Growth and morphological changes in the small and the large intestine in piglets during the first three days after birth.J Dev Physiol 1992;18:161.
[97]Cranwell PD.Development of the neonatal gut and enzyme systems.In:The neonatal Pig Development and Survival CAB International.1995:55.
[98]顾宪红,张宏福.断奶日龄对仔猪肠道黏膜水解酶及其上皮间淋巴细胞和杯状细胞数的影响.动物营养学报,2005年1期.
[99]王艳玲.仔猪断奶前后消化酶活性变化的初步探讨.中国畜牧杂志,2005.2005:29-32
[100]Buccigrossi V,de Marco G,Bruzzese E,Ombrato L,Bracale I,Polito G,Guarino A.Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation.Pediatr Res 2007;61:410.
[101]Zhao SH,Nettleton D,Liu W,Fitzsimmons C,Ernst CW,Raney NE,Tuggle CK.Complementary DNA macroarray analyses of differential gene expression in porcine fetal and postnatal muscle.J Anita Sci 2003;81:2179.
[102]Master SR,Hartman JL,D'Cruz CM,Moody SE,Keiper EA,Ha SI,Cox JD,Belka GK,Chodosh LA.Functional microarray analysis of mammary organogenesis reveals a developmental role in adaptive thermogenesis.Mol Endocrinol 2002;16:1185.
[103]Zhao SH,Recknor J,Lunney JK,Nettleton D,Kuhar D,Orley S,Tuggle CK.Validation of a first-generation long-oligonucleotide microarray for transcriptional profilinlg in the pig.Genomics 2005;86:618.
[104]Curtis RK,Oresic M,Vidal-Puig A.Pathways to the analysis of microarray data.Trends Biotechnol 2005;23:429.
[105]Herskowitz I.MAP kinase pathways in yeast:for mating and more.Cell 1995;80:187.
[106]Axmann A,Seidel D,Reirnann T,Hempel U,Wenzel KW.Transforming growth factor-betal-induced activation of the Raf-MEK-MAPK signaling pathway in rat lung fibroblasts via a PKC-dependent mechanism.Biochem Biophys Res Commun 1998;249:456.
[107]Surachetpong W,Singh N,Cheung KW,Luckhart S.MAPK ERK signaling regulates the TGF-betal-dependent mosquito response to Plasmodium falciparum.PLoS Pathog 2009;5:e1000366.
[108]Choi ME.Mechanism of transforming growth factor-betal signaling.Kidney Int Suppl 2000;77:S53.
[109]Megason SG,Fraser SE.Imaging in systems biolosy.Cell 2007;130:784.
[110]Verwei M,van den Berg H,Havenaar R,Groten JP.Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells.Eur J Nutr 2005;44:242.
[111]Piedrahita JA,Oetama B,Bennett GD,van Waes J,Kamen BA,Richardson J,Lacey SW,Anderson RG,Finnell RH.Mice lacking the folic acid-binding protein Folbpl are defective in early embryonic development.Nat Genet 1999;23:228.
[112]张振峰,高红亮,蔡在龙,毛积芳,焦炳华.小鼠肝脏部分耐热蛋白的初步研究.第二大学学报2004;2.
[113]Beisel C,Imhof A,Greene J,Kremmer E,Sauer F.Histone methylation by the Drosophila epigenetic transcriptional regulator Ashl.Nature 2002;419:857.
[114]邢婉丽,程京著,生物芯片技术.清华大学出版社,2004
[115]Hampson DJ.Attempts to modify changes in the piglet small intestine after weaning.Res Vet sci 1986;40:313.
[116]Kiarie E,Nyachoti CM,Slominski BA,Blank G.Growth performance,gastrointestinal microbial activity,and nutrient digestibility in early-weaned pigs fed diets containing flaxseed and carbohydrase enzyme.J Anim Sci 2007;85:2982.
[117]霍永久.酪蛋白酶解产物对新生仔猪胃肠道生长发育的影响,扬州大学学报(农业与生命科学版)2006年4期.
[118]赵念,张莉莉.添加酪蛋白酶解物对宫内生长迟缓仔猪肠道生长发育的影响.南京农业大学学报,2006年3期
[119]Kim JH,Heo KN,Odle J,Han K,Harrell RJ.Liquid diets accelerate the growth of early-weaned pigs and the effects are maintained to market weight.J Anita Sci 2001;79:427.
[120]Pluske JR,Siba PM,Pethick DW,Durmic Z,Mullan BP,Hampson DJ.The incidence of swine dysentery in pigs can be reduced by feeding diets that limit the amount of fermentable substrate entering the large intestine.J Nutr 1996;126:2920.
[121]Pluske JR,Thompson MJ,Atwood CS,Bird PH,Williams IH,Hartmann PE.Maintenance of villus height and crypt depth,and enhancement of disaccharide digestion and monosaccharide absorption,in piglets fed on cows' whole milk after weaning.Br J Nutr 1996;76:409.
[122]李明洲.脂肪型和瘦肉型猪肌肉生长和脂肪沉积相关基因的差异表达分析和分子网络构建.自然科学进展,2008,18(2):134-144.
[123]Hayesmoore JB,Bray NJ,Cross WC,Owen MJ,O'Donovan MC,Morris HR.The effect of age and the H1c MAPT haplotype on MAPT expression in human brain.Neurobiol Aging 2008.
[2]刘量衡.物质、信息、生命:中山大学出版社2001.
[3]Moughan PJ,Birtles M J,Cranwell PD,Smith WC,Pedraza M.The piglet as a model animal for studying aspects of digestion and absorption in milk-fed human infants.World Rev Nutr Diet 1992;67:40.
[4]Nabuurs MJ.Weaning piglets as a model for studying pathophysiology of diarrhea.Vet Q 1998;20Suppl 3:S42.
[5]Rothschild MF.Advances in pig genomics and functional gene discovery.Comp Funct Genomics 2003;4:266.
[6]Rothschild MF.Porcine genomics delivers new tools and results:this little piggy did more than just go to market.Genet Res 2004;83:1.
[7]Domeneghini C,Di Giancamillo A,Arrighi S,Bosi G.Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism.State of the art in the pig,and perspectives towards humans.Histol Histopathol 2006;21:273.
[8]Eubanks DL,Cooper R,Boring JG.Surgical technique for long-term cecal cannulation in the Yucatan minipig(Sus scrofa domestica).J Am Assoc Lab Anim Sci 2006;45:52.
[9]Reid G,Sanders ME,Gaskins HR,Gibson GR,Mercenier A,Rastall R,Roberfroid M,Rowland I,Cherbut C,Klaenhammer TR.New scientific paradigms for probiotics and prebiotics.J Clin Gastroenterol 2003;37:105.
[10]Society tAC.Cancer medicine.Hamilton.London,2003.
[11]王喜忠.细胞生物学.高等教育出版社2000.
[12]陆承平.兽医微生物学,中国农业出版社,2001.
[13]Cranwell PD.Development of the neonatal gut and enzyme systems,1995.
[14]王镜岩.生物化学:高等教育出版社,1999.
[15]北野宏明(日),刘笔锋(译).系统生物学基础:化学工业出版社,2007.
[16]Hiendleder S,Bauersachs S,Boulesteix A,Blum H,Arnold GJ,Frohlich T,Wolf E.Functional genomics:tools for improving farm animal health and welfare.Rev Sci Tech 2005;24:355.
[17]孙之荣(译),马尔科姆.坎贝尔.探索基因组学、蛋白组学和生物信息学,科学出版社出版,2005.
[18]Wintero AK,Fredholm M,Davies W.Evaluation and characterization of a porcine small intestine cDNA library:analysis of 839 clones.Mamm Genome 1996;7:509.
[19]Wernersson R,Schierup MH,Jorgensen FG,Gorodkin J,Panitz F,Staerfeldt HH,Christensen OF,Mailund T,Hornshoj H,Klein A,Wang J,Liu B,Hu S,Dong W,Li W,Wong GK,Yu J,Bendixen C,Fredholm M,Brunak S,Yang H,Bolund L.Pigs in sequence space:a 0.66X coverage pig genome survey based on shotgun sequencing.BMC Genomics 2005;6:70.
[20]Zhang H,Malo C,Boyle CR,Buddington RK.Diet influences development of the pig(Sus scrofa)intestine during the first 6 hours after birth.J Nutr 1998;128:1302.
[21]Zhang H,Malo C,Buddington RK.Suckling induces rapid intestinal growth and changes in brush border digestive functions of newborn pigs.J Nutr 1997;127:418.
[22]van Beers-Schreurs HM,Nabuurs MJ,Vellenga L,Kalsbeek-van der Valk HJ,Wensing T,Breukink HJ.Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood.J Nutr 1998;128:947.
[23]Tang M,Laarveld B,Van Kessel AG,Hamilton DL,Estrada A,Patience JF.Effect of segregated early weaning on postweaning small intestinal development in pigs.J Anim Sci 1999;77:3191.
[24]Inoue R,Tsukahara T,Nakanishi N,Ushida K.Development of the intestinal microbiota in the piglet.J Gen Appl Microbiol 2005;51:257.
[25]Thompson CL,Wang B,Holmes AJ.The immediate environment during postnatal development has long-term impact on gut community structure in pigs.ISME J 2008.
[26]Dvorak CM,Hirsch GN,Hyland KA,Hendrickson JA,Thompson BS,Rutherford MS,Murtaugh MP.Genomic dissection of mucosal immunobiology in the porcine small intestine.Physiol Genomics 2006;28:5.
[27] Trahair JF, Harding R. Ultrastructural anomalies in the fetal small intestine indicate that fetal swallowing is important for normal development: an experimental study. Virchows Arch A Pathol Anat Histopathol 1992;420:305.
[28] Kelly D, King TP, McFadyen M, Travis AJ. Effect of lactation on the decline of brush border lactase activity in neonatal pigs. Gut 1991;32:386.
[29] Blass EM, Teicher MH. Suckling. Science 1980;210:15.
[30] Hamosh M. Protective function of proteins and lipids in human milk. Biol Neonate 1998;74:163.
[31] James PS, Smith MW, Tivey DR, Wilson TJ. Dexamethasone selectively increases sodium-dependent alanine transport across neonatal piglet intestine. J Physiol 1987;393:569.
[32] Litin BS, Swan KR, Koldovsky O. Hormone maturative effect on perinatal rat colon glycosidases. J Pediatr Gastroenterol Nutr 1983;2:133.
[33] Plateroti M, Gauthier K, Domon-Dell C, Freund JN, Samarut J, Chassande O. Functional interference between thyroid hormone receptor alpha (TRalpha) and natural truncated TRDeltaalpha isoforms in the control of intestine development. Mol Cell Biol 2001;21:4761.
[34] Durant M, Gargosky SE, Dahlstrom KA, Hellman BH, Jr., Castillo RO. Regulation of postnatal intestinal maturation by growth hormone: studies in rats with isolated growth hormone deficiency. Pediatr Res 1996;40:88.
[35] W.N.Ewing, D.J.A.Cole, editors, the living gut, 1994.
[36] Domeneghini C, Di Giancamillo A, Savoini G, Paratte R, Bontempo V, Dell'Orto V. Structural patterns of swine ileal mucosa following L-glutamine and nucleotide administration during the weaning period. An histochemical and histometrical study. Histol Histopathol 2004;19:49.
[37] Madej M, Lundh T, Lindberg JE. Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets. Biol Neonate 1999;75:250.
[38] Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM. Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr 2008;138:24.
[39] Wu G. Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol 1997;272:G1382.
[40] Loret S, Brolet P, Pierzynowski S, Gouders I, Klimek M, Danielson V, Rosted A, Lesniewska V, Dandrifosse G. Pancreatic exocrine secretions as a source of luminal polyamines in pigs. Exp Physiol 2000;85:301.
[41] Tappenden KA, Albin DM, Bartholome AL, Mangian HF. Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story. J Nutr 2003;133:3717.
[42] Chowdhury SR, King DE, Willing BP, Band MR, Beever JE, Lane AB, Loor JJ, Marini JC, Rund LA, Schook LB, Van Kessel AG, Gaskins HR. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 2007;8:215.
[43] Maxwell SM. Sudden onset of blurred vision in a thirteen-year-old girl. Pediatr Infect Dis J 1995;14:1016.
[44] Kelly D, King TP, McFadyen M, Courts AG. Effect of preclosure colostrum intake on the development of the intestinal epithelium of artificially reared piglets. Biol Neonate 1993;64:235.
[45] 张宏福．仔猪营养生理与饲料配制技术研究,中国农业科技出版社,2000．
[46] Rawls JF, Samuel BS, Gordon JI. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci U S A 2004;101:4596.
[47] Su Y, Yao W, Perez-Gutierrez ON, Smidt H, Zhu WY. Changes in abundance of Lactobacillus spp. and Streptococcus suis in the stomach, jejunum and ileum of piglets after weaning. FEMS Microbiol Ecol 2008;66:546.
[48] Beagley KW, Husband AJ. Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 1998;18:237.
[49] 张宏福,李长忠．不同断奶日龄对仔猪消化酶发育规律的研究．中国农业科技出版社,2000．
[50] Bikker P, Dirkzwager A, Fledderus J, Trevisi P, le Huerou-Luron I, Lalles JP, Awati A. The effect of dietary protein and fermentable carbohydrates levels on growth performance and intestinal characteristics in newly weaned piglets. J Anim Sci 2006;84:3337.
[51] Garcia-Rodenas CL, Bergonzelli GE, Nutten S, Schumann A, Cherbut C, Turini M, Ornstein K, Rochat F, Corthesy-Theulaz I. Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J Pediatr Gastroenterol Nutr 2006;43:16.
[52] Helm RM, Golden C, McMahon M, Thampi P, Badger TM, Nagarajan S. Diet regulates the development of gut-associated lymphoid tissue in neonatal piglets.Neonatology 2007;91:248.
[53]Gilbert ER,Li H,Emmerson DA,Webb KE,Jr.,Wong EA.Dietary protein quality and feed restriction influence abundance of nutrient transporter mRNA in the small intestine of broiler chicks.J Nutr 2008;138:262.
[54]McCracken BA,Spurlock ME,Roos MA,Zuckermann FA,Gaskins HR.Weaning anorexia may contribute to local inflammation in the piglet small intestine.J Nutr 1999;129:613.
[55]Hampson DJ.Alterations in piglet small intestinal structure at weaning.Res Vet Sci 1986;40:32.
[56]Hall GA,Byrne TF.Effects of age and diet on small intestinal structure and function in gnotobiotic piglets.Res Vet Sci 1989;47:387.
[57]Mathers JC.Nutrient regulation of intestinal proliferation and apoptosis.Proc Nutr Soc 1998;57:219.
[58]Sanderson IR.Dietary regulation of genes expressed in the developing intestinal epithelium.Am J Clin Nutr 1998;68:999.
[59]Klurfeld DM.Nutritional regulation of gastrointestinal growth.Front Biosci 1999;4:D299.
[60]Wang J,Chen L,Li P,Li X,Zhou H,Wang F,Li D,Yin Y,Wu G.Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation.J Nutr 2008;138:1025.
[61]Reeds PJ,Burrin DG.Glutamine and the bowel.J Nutr 2001;131:25055.
[62]Biagi G,Piva A,Moschini M,Vezzali E,Roth FX.Effect of gluconic acid on piglet growth performance,intestinal microflora,and intestinal wall morphology.J Anim Sci 2006;84:370.
[63]李德发.猪的营养.中国农业科学技术出版社,2002.
[64]Makkink CA,Berntsen PJ,op den Kamp BM,Kemp B,Verstegen MW.Gastric protein breakdown and pancreatic enzyme activities in response to two different dietary protein sources in newly weaned pigs.J Anim Sci 1994;72:2843.
[65]Makkink CA,Negulescu GP,Qin G,Verstegen MW.Effect of dietary protein source on feed intake,growth,pancreatic enzyme activities and jejunal morphology in newly-weaned piglets.Br J Nutr 1994;72:353.
[66]E.Klipp,R.Herwig,A.Kowald,贺福初(译).系统生物学的理论、方法和应用.2007.
[67]Kitano H.Systems biology:a brief overview.Science 2002;295:1662.
[68]Kitano Ho Systems Biology:Toward System-level Understanding of Biological Systems.2001.
[69]Fields S,Song O.A novel genetic system to detect protein-protein interactions.Nature 1989;340:245.
[70]李瑶.基因芯片数据分析与处理:化学工业出版社,2006.
[71]Hood L,Heath JR,Phelps ME,Lin B.Systems biology and new technologies enable predictive and preventative medicine.Science 2004;306:640.
[72]Oltvai ZN,Barabasi AL.Systems biology.Life's complexity pyramid.Science 2002;298:763.
[73]Castrillo JI,Oliver SG.Yeast as a touchstone in post-genomic research:strategies for integrative analysis in functional genomics.J Biochem Mol Biol 2004;37:93.
[74]Millard AD,Tiwari B.Oligonucleotide microarrays for bacteriophage expression studies.Methods Mol Biol 2009;502:193.
[75]Li X,Zhu J,Huo H.Profile of differentially expressed genes in blood vessels and blood cells of hyperlipidemia rats using suppression subtractive hybridization.J Nanosci Nanotechnol 2005;5:1287.
[76]Tang Z.LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs.Genome Biology 2007;Volume 8,Issue 6,Article R115.
[77]Hoth S,Ikeda Y,Morgante M,Wang X,Zuo J,Hanafey MK,Gaasterland T,Tingey SV,Chua NH.Monitoring genome-wide changes in gene expression in response to endogenous cytokinin reveals targets in Arabidopsis thaliana.FEBS Lett 2003;554:373.
[78]Spinella DG,Bernardino AK,Redding AC,Koutz P,Wei Y,Pratt EK,Myers KK,Chappell G,Gerken S,McConnell SJ.Tandem arrayed ligation of expressed sequence tags(TALEST]:a new method for generating global gene expression profiles.Nucleic Acids Res 1999;27:e22.
[79]Tang Z.LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs.Genome Biology 2007;Volume 8,Issue 6,Article R115.
[80]杨志超.基于时间序列表达数据基因调控网络模型的研究进展.第二军医大学学报2008.
[81]Ernst J,Nau GJ,Bar-Joseph Z.Clustering short time series gene expression data.Bioinformatics 2005;21 Suppl 1:i159.
[82]Ramoni MF,Sebastiani P,Kohane IS.Cluster analysis of gene expression dynamics.Proc Natl Acad Sci U S A 2002;99:9121.
[83]Schliep A,Costa IG,Steinhoff C,Schonhuth A.Analyzing gene expression time-courses.IEEE/ACM Trans Comput Biol Bioinform 2005;2:179.
[84]Gotz S,Garcia-Gomez JM,Terol J,Williams TD,Nagaraj SH,Nueda MJ,Robles M,Talon M,Dopazo J,Conesa A.High-throughput functional annotation and data mining with the Blast2GO suite.Nucleic Acids Res 2008.
[85]Ashburner M,Ball CA,Blake JA,Botstein D,Butler H,Cherry JM,Davis AP,Dolinski K,Dwight SS,Eppig JT,Harris MA,Hill DP,Issel-Tarver L,Kasarskis A,Lewis S,Matese JC,Richardson JE,Ringwald M,Rubin GM,Sherlock G.Gene ontology:tool for the unification of biology.The Gene Ontology Consortium.Nat Genet 2000;25:25.
[86]Tomita M,Hashimoto K,Takahashi K,Shimizu TS,Matsuzaki Y,Miyoshi F,Saito K,Tanida S,Yugi K,Venter JC,Hutchison CA,3rd.E-CELL:software environment for whole-cell simulation.Bioinformatics 1999;15:72.
[87]Kanehisa M,Goto S.KEGG:kyoto encyclopedia of genes and genomes.Nucleic Acids Res 2000;28:27.
[88]Dahlquist KD,Salomonis N,Vranizan K,Lawlor SC,Conklin BR.GenMAPP,a new tool for viewing and analyzing microarray data on biological pathways.Nat Genet 2002;31:19.
[89]Suderman M,Hallett M.Tools for visually exploring biological networks.Bioinformatics 2007;23:2651.
[90]pevsner J,.生物信息学与功能基因组学:Chemical industry press,2006.
[91]Gonzalez G,Uribe JC,Tari L,Brophy C,Baral C.Mining gene-disease relationships from biomedical literature:weighting protein-protein interactions and connectivity measures.Pac Symp Biocomput 2007:28.
[92]YH Y,T S.Design issues for cDNA microarray experiments.Nat Rev Genet 2002;3:9.
[93]Chuaqui RF,Bonner RF,Best CJ,Gillespie JW,Flaig MJ,Hewitt SM,Phillips JL,Krizman DB,Tangrea MA,Ahram M,Linehan WM,Knezevic V,Emmert-Buck MR.Post-analysis follow-up and validation of microarray experiments.Nat Genet 2002;32 Suppl:509.
[94]Barrett T,Troup DB,Wilhite SE,Ledoux P,Rudnev D,Evangelista C,Kim IF,Soboleva A,Tomashevsky M,Edgar R.NCBI GEO:mining tens of millions of expression profiles—database and tools update.Nucleic Acids Res 2007;35:D760.
[95]霍永久.新生仔猪小肠生长发育及肠黏膜部分基 因的表达 南京农业大学学报2005:129-132
[96]Xu RJ,Mellor DJ,Tungthanathanich P,Birtles MJ,Reynolds GW,Simpson HV.Growth and morphological changes in the small and the large intestine in piglets during the first three days after birth.J Dev Physiol 1992;18:161.
[97]Cranwell PD.Development of the neonatal gut and enzyme systems.In:The neonatal Pig Development and Survival CAB International.1995:55.
[98]顾宪红,张宏福.断奶日龄对仔猪肠道黏膜水解酶及其上皮间淋巴细胞和杯状细胞数的影响.动物营养学报,2005年1期.
[99]王艳玲.仔猪断奶前后消化酶活性变化的初步探讨.中国畜牧杂志,2005.2005:29-32
[100]Buccigrossi V,de Marco G,Bruzzese E,Ombrato L,Bracale I,Polito G,Guarino A.Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation.Pediatr Res 2007;61:410.
[101]Zhao SH,Nettleton D,Liu W,Fitzsimmons C,Ernst CW,Raney NE,Tuggle CK.Complementary DNA macroarray analyses of differential gene expression in porcine fetal and postnatal muscle.J Anita Sci 2003;81:2179.
[102]Master SR,Hartman JL,D'Cruz CM,Moody SE,Keiper EA,Ha SI,Cox JD,Belka GK,Chodosh LA.Functional microarray analysis of mammary organogenesis reveals a developmental role in adaptive thermogenesis.Mol Endocrinol 2002;16:1185.
[103]Zhao SH,Recknor J,Lunney JK,Nettleton D,Kuhar D,Orley S,Tuggle CK.Validation of a first-generation long-oligonucleotide microarray for transcriptional profilinlg in the pig.Genomics 2005;86:618.
[104]Curtis RK,Oresic M,Vidal-Puig A.Pathways to the analysis of microarray data.Trends Biotechnol 2005;23:429.
[105]Herskowitz I.MAP kinase pathways in yeast:for mating and more.Cell 1995;80:187.
[106]Axmann A,Seidel D,Reirnann T,Hempel U,Wenzel KW.Transforming growth factor-betal-induced activation of the Raf-MEK-MAPK signaling pathway in rat lung fibroblasts via a PKC-dependent mechanism.Biochem Biophys Res Commun 1998;249:456.
[107]Surachetpong W,Singh N,Cheung KW,Luckhart S.MAPK ERK signaling regulates the TGF-betal-dependent mosquito response to Plasmodium falciparum.PLoS Pathog 2009;5:e1000366.
[108]Choi ME.Mechanism of transforming growth factor-betal signaling.Kidney Int Suppl 2000;77:S53.
[109]Megason SG,Fraser SE.Imaging in systems biolosy.Cell 2007;130:784.
[110]Verwei M,van den Berg H,Havenaar R,Groten JP.Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells.Eur J Nutr 2005;44:242.
[111]Piedrahita JA,Oetama B,Bennett GD,van Waes J,Kamen BA,Richardson J,Lacey SW,Anderson RG,Finnell RH.Mice lacking the folic acid-binding protein Folbpl are defective in early embryonic development.Nat Genet 1999;23:228.
[112]张振峰,高红亮,蔡在龙,毛积芳,焦炳华.小鼠肝脏部分耐热蛋白的初步研究.第二大学学报2004;2.
[113]Beisel C,Imhof A,Greene J,Kremmer E,Sauer F.Histone methylation by the Drosophila epigenetic transcriptional regulator Ashl.Nature 2002;419:857.
[114]邢婉丽,程京著,生物芯片技术.清华大学出版社,2004
[115]Hampson DJ.Attempts to modify changes in the piglet small intestine after weaning.Res Vet sci 1986;40:313.
[116]Kiarie E,Nyachoti CM,Slominski BA,Blank G.Growth performance,gastrointestinal microbial activity,and nutrient digestibility in early-weaned pigs fed diets containing flaxseed and carbohydrase enzyme.J Anim Sci 2007;85:2982.
[117]霍永久.酪蛋白酶解产物对新生仔猪胃肠道生长发育的影响,扬州大学学报(农业与生命科学版)2006年4期.
[118]赵念,张莉莉.添加酪蛋白酶解物对宫内生长迟缓仔猪肠道生长发育的影响.南京农业大学学报,2006年3期
[119]Kim JH,Heo KN,Odle J,Han K,Harrell RJ.Liquid diets accelerate the growth of early-weaned pigs and the effects are maintained to market weight.J Anita Sci 2001;79:427.
[120]Pluske JR,Siba PM,Pethick DW,Durmic Z,Mullan BP,Hampson DJ.The incidence of swine dysentery in pigs can be reduced by feeding diets that limit the amount of fermentable substrate entering the large intestine.J Nutr 1996;126:2920.
[121]Pluske JR,Thompson MJ,Atwood CS,Bird PH,Williams IH,Hartmann PE.Maintenance of villus height and crypt depth,and enhancement of disaccharide digestion and monosaccharide absorption,in piglets fed on cows' whole milk after weaning.Br J Nutr 1996;76:409.
[122]李明洲.脂肪型和瘦肉型猪肌肉生长和脂肪沉积相关基因的差异表达分析和分子网络构建.自然科学进展,2008,18(2):134-144.
[123]Hayesmoore JB,Bray NJ,Cross WC,Owen MJ,O'Donovan MC,Morris HR.The effect of age and the H1c MAPT haplotype on MAPT expression in human brain.Neurobiol Aging 2008.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |